Method for collecting a desired blood component and performing a photopheresis treatment

ABSTRACT

An improved method for separating whole blood into components and collecting a desired blood component. The method allows a desired blood component to be subjected to centrifugal forces within a separator for prolonged periods of time, yielding a cleaner cut and higher yield of the desired blood component. Whole blood is drawn from a source and pumped into a separator, the undesired blood components are removed from the separator at rates so as to build up the desired blood component in the separator. The desired blood component is only removed after a predetermined amount of the desired blood component has built up in the separator. It is preferred that the desired blood component be buffy coat and that the method be used to perform photopheresis treatments. In another aspect, the invention is a method of performing a full photopheresis treatment to treat diseases in a reduced time, preferably less than about 70 minutes, and more preferably less than about 45 minutes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.10/654,803 filed Sep. 3, 2003, continuation-in-part application of U.S.patent application Ser. No. 10/375,629, filed Feb. 27, 2003, whichclaims the benefit of U.S. Provisional Application Ser. No. 60/361,287,filed Mar. 4, 2002, both of which are hereby incorporated by referencein their entireties.

TECHNICAL FIELD OF THE INVENTION

The present invention relates generally to methods for separating wholeblood into blood components and collecting a desired blood component,and specifically to methods of treating diseases with a photopheresistreatment.

BACKGROUND OF THE INVENTION

Several treatments for disease require the removal of blood from apatient, processing the one or more components of the blood, and returnof the processed components for a therapeutic effect. Thoseextracorporeal treatments require systems for safely removing blood fromthe patient, separating it into components, and returning the blood orblood components to the patient. With the advance of medical sciences,it has become possible to treat a patient's blood in closed-loopprocesses, returning the patient's own treated blood back to him in onemedical treatment. An example of such processes include externaltreatment methods for diseases in which there is a pathological increaseof lymphocytes, such as cutaneous T-cell lymphoma or other diseasesaffecting white blood cells. In such methods, the patient's blood isirradiated with ultraviolet light in the presence of a chemical or anantibody. Ultraviolet light affects the bonding between the lymphocytesand the chemical or antibody that inhibits the metabolic processes ofthe lymphocytes.

Photopheresis systems and methods have been proposed and used whichinvolve separation of buffy coat from the blood, addition of aphotoactivatable drug, and UV irradiation of the buffy coat beforere-infusion to the patient. Extracorporeal photopheresis may be utilizedto treat numerous diseases including Graft-versus-Host disease,Rheumatoid Arthritis, Progressive Systematic Sclerosis, Juvenile OnsetDiabetes, Inflammatory Bowel Disease and other diseases that are thoughtto be T-cell or white blood cell mediated, including cancer. Apheresissystems and methods have also been proposed and used which involveseparation of blood into various components.

During one of these medical treatments, a centrifuge bowl, such as, forexample, a Latham bowl, as shown in U.S. Pat. No. 4,303,193, expresslyincorporated by reference in its entirety herein, is operated toseparate whole blood into red blood cells (“RBCs”), plasma, and buffycoat. The Latham bowl is a blood component separator that has been usedfor some time in the medical apheresis market as well as in innovativemedical therapies such as extracorporeal photopheresis (ECP). PCTApplications WO 97/36581 and WO 97/36634, and U.S. Pat. Nos. 4,321,919;4,398,906; 4,428,744; and 4,464,166 provide descriptions ofextracorporeal photopheresis, and are hereby expressly incorporated byreference in their entirety.

Latham bowl efficiency is often measured by the white blood cell (“WBC”)“yield,” which is typically about 50%. Yield is defined as thepercentage of cells collected versus the number processed. When comparedto other types of whole blood separators, this high yield enables theLatham bowl separator to collect much larger volumes of WBCs whileprocessing much less whole blood from the donor patient. However, amajor drawback to the Latham bowl separator is that the separationprocess must be repeatedly stopped to remove the packed RBCs and plasmaonce they fill the inside of the bowl, creating a “batch-type” treatmentprocess. Although the Latham bowl separator has a high volume yield, theconstant filling and emptying of this bowl wastes time; thus, theprocess is considered less efficient with respect to time.

Prior photopheresis and apheresis systems and methods usually requirebatch processes and therefore take several hours to treat a patient orto obtain a sufficient supply of separated blood fragments. Furthermore,the systems are very complex to manufacture. It is a constant objectiveto reduce the time it takes to perform a complete photopheresistreatment session. Another objective is to reduce the amount of bloodthat must be drawn form a patient and processed in closed-loop processesper photopheresis treatment session. Yet another objective to increasethe amount of white blood cell yield or obtain a cleaner cut of buffycoat per volume of whole blood processed.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide an improved method forseparating a fluid, such as blood or other biological fluid, into itscomponents. An additional object is to increase the efficiency ofcurrent fluid separation processes by decreasing the time necessary toseparate out a desired amount of a fluid component from the fluid. Yetother objects of the present invention are to treat a patient moreefficiently, to improve a photopheresis process, or to improve aplatelet removal process. An additional object of the present inventionis to separate and remove targeted cells by their specific gravity.Another object of the present invention is to eliminate the need toperform fluid separation processes in “batch” form. A still furtherobject of the present invention is to increase the percent yield of adesired fluid component from a fluid being separated.

The present invention solves the inadequacies of the prior art by beingable to continuously separate fluid components without interrupting theprocess to empty a centrifuge bowl and remove a separated component.Thus, the present invention eliminates batch processing and other Lathambowl batch-type techniques. These objects and others are met by thepresent invention which is directed at improving the methods forseparating whole blood into its components and collecting a desiredblood component. Depending on the intended treatment, the desired bloodcomponent may be buffy coat, red blood cells, plasma, or any componentthereof. The present invention is also directed at improving existingmethods of treating diseases using photopheresis therapies.Specifically, the present invention provides a continuous process forwhole blood separation of sufficient fragment for photopheresistreatment so as to greatly reduce the photopheresis treatment time for apatient.

When it is desired to collect buffy coat from whole blood, the inventionin one aspect is a method comprising: providing a separator having aninlet, a first outlet, and a second outlet; drawing whole blood from asource; adding an anticoagulant fluid to the whole blood in apredetermined ratio to form a mixture of whole blood and anticoagulantfluid; pumping the mixture of whole blood and anticoagulant fluid intothe separator via the inlet at a selected inlet rate; separating themixture into blood components of different densities; withdrawing plasmaand red blood cells from the separator while continuing to pump themixture of whole blood and anticoagulant fluid into the separator, theplasma and red blood cells being withdrawn at rates so as to build upbuffy coat in the separator, the plasma being withdrawn via the firstoutlet and the red blood cells being withdrawn via the second outlet;and upon a predetermined amount of buffy coat building up in theseparator, collecting the buffy coat from the separator.

By withdrawing the red blood cells and the plasma at rates so that thebuffy coat is allowed to build up within the separator, which ispreferably a centrifuge bowl, the buffy coat is subjected to thecentrifugal force of the separator for a prolonged period of time.Increasing the time which the buffy coat is subjected to centrifugalforce yields a cleaner fraction of buffy coat and an increased whiteblood cell yield. Additionally, this prolonged exposure can be used tofurther separate the buffy coat into its constituent parts, includingplatelets and various kinds of leukocytes.

When pumping the mixture of whole blood and anticoagulant fluid into theseparator, it is preferred that the mixture pass through, and be routedby, a cassette for controlling fluid flow. It is further preferable thatthe buffy coat be collected from the separator by discontinuing thewithdrawal of red blood cells from the second outlet, thereby causingthe red blood cells to push the buffy coat out of the separator via thefirst outlet as whole blood continues to enter the separator. Thewithdrawn buffy coat can be collected in a treatment bag that is fluidlyconnected to the separator via an outlet line. In this embodiment, thecollection of buffy coat is preferably discontinued when red blood cellsare detected in the outlet line. This will minimize red blood cells frombeing mixed with the desired buffy coat.

In performing this method, it is also preferable that only the plasma bewithdrawn from the separator until a predetermined amount of red bloodcells are detected in the separator. Then, upon the predetermined amountof red blood cells being detected in the separator, the red blood cellswill be drawn from the separator at a rate so as to maintain the amountof red blood cells present in the separator at approximately thepredetermined amount. The predetermined amount of red blood cells can bedetected using a hematocrit sensor that can detect a red cell linewithin the centrifuge bowl itself.

When the method is being used in a closed loop process where the sourceof the whole blood is a patient, it is important to return fluids backto the patient during processing. In order to achieve this, it ispreferable that the withdrawn plasma be collected in a plasma storagebag, mixed with a priming fluid, and returned to the patient when aselected amount of plasma is collected in the plasma storage bag. It isfurther preferable to mix the withdrawn red blood cells with the plasmaand priming fluid mixture from the plasma collection bag and returningthe red blood cell-plasma-priming fluid mixture to the patient at a rateapproximately equal to the inlet rate.

This method can be used in connection with photopheresis treatment. In aphotopheresis treatment, the method will further comprise injecting aphotoactivation chemical into the collected buffy coat, and irradiatingthe collected buffy coat within an irradiation chamber until apredetermined amount of energy has been transferred to the collectedbuffy coat. In order to ensure that a proper amount of energy istransferred to the buffy coat, for example to induce apoptosis, it ispreferable to recirculate the collected buffy coat between a treatmentbag and the irradiation chamber. Before the irradiated buffy coat isreturned to the patient undergoing the photopheresis therapy, theirradiated buffy coat should pass through a filter. Using this method,enough buffy coat can be collected and irradiated to perform a fullphotopheresis treatment in less than about 70 minutes. More preferably,the overall treatment time is less than about 45 minutes.

It may also be desired to collect the red blood cells from the separatorfor other types of treatments. Because the red blood cells can besubjected to prolonged centrifugal force, the current method provides avery packed amount of red cells. These red blood cells can be withdrawnand collected for further use, such as in apheresis therapy.

In yet another aspect, the invention is a method of performing aphotopheresis treatment for ameliorating diseases. This methodcomprises: drawing whole blood from a source; adding an anticoagulantfluid to the whole blood in a predetermined ratio to form a mixture ofthe whole blood and the anticoagulant fluid; separating the mixture ofwhole blood and anticoagulant into a plurality of blood componentsaccording to density; mixing a photoactivation chemical with at leastone the blood components to form a mixture of the photoactivationchemical and the at least one blood component; irradiating thecombination of the at least one blood component and photoactivationchemical; and returning the irradiated combination to a patient; whereinthe entire photopheresis treatment is completed in less about than 70minutes. More preferably, the entire photopheresis treatment iscompleted in less about than 45 minutes. This is a vast improvement overprevious photopheresis treatments which usually required a treatmenttime of two hours or more.

In this aspect of the invention, the at least one blood component can bebuffy coat, a leukocyte, or platelets. Buffy coat is preferred. Inperforming the photopheresis treatment, the mixture of whole blood andanticoagulant fluid is preferably pumped into a separator having aninlet, a first outlet, and a second outlet. Because buffy coat is thedesired blood component in a photopheresis therapy session, plasma andred blood cells are withdrawn from the separator while continuing topump the mixture of whole blood and anticoagulant fluid into theseparator. The plasma and red blood cells are preferably withdrawn atrates so as to build up buffy coat in the separator, allowing the buffycoat to be exposed to prolonged centrifugal forces. The plasma iswithdrawn via the first outlet and the red blood cells being withdrawnvia the second outlet. Buffy coat is preferably collected from theseparator for irradiation only after a predetermined amount of buffycoat builds up therein.

The separated buffy coat is preferably collected from the separatorthrough an outlet line that is fluidly connected to a treatment bag. Thebuffy coat can be collected from the separator by discontinuing thewithdrawal of red blood cells from the second outlet while continuing topump in whole blood. This causes the red blood cells to push the buffycoat out of the separator via the first outlet. Buffy coat collection ispreferably stopped when red blood cells are detected in the outlet lineby a hematocrit sensor. The collected buffy coat is preferablyirradiated within an irradiation chamber until a predetermined amount ofenergy has been transferred to the collected buffy coat. Thepredetermined amount of energy is preferably sufficient to induceapoptosis.

This photopheresis treatment is preferably performed in a closed-loopsystem where the patient is also the source. Finally, instead ofseparating only buffy coat, the buffy cells can be further separated ifdesired into their components such as platelets and leukocytes.

Finally, an effective method of collecting red blood cells is achievedby another aspect of the invention which is a method of collecting adesired blood component comprising: providing a separator having aninlet, a first outlet, and a second outlet; drawing whole blood from asource; adding an anticoagulant fluid to the whole blood in apredetermined ratio to form a mixture of whole blood and anticoagulantfluid; pumping the mixture of whole blood and anticoagulant fluid intothe separator via the inlet at a selected inlet rate; separating themixture into blood components of different densities; withdrawing plasmaand buffy coat from the separator while continuing to pump the mixtureof whole blood and anticoagulant fluid into the separator, the plasmaand buffy coat being withdrawn at rates so as to build up red bloodcells in the separator, the plasma and buffy coat being withdrawn viathe first outlet; and upon a predetermined amount of red blood cellsbuilding up in the separator, collecting the red blood cells from theseparator via the second outlet. This method allows the red blood cellsto build up in the separator and be subjected to a maximum amount ofprolonged centrifugal force

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described in detail with respect to the accompanyingdrawings, which illustrate an embodiment of the inventive apparatus,assemblies, systems, and methods.

FIG. 1 is a schematic representation of an embodiment of a disposablekit for use in photopheresis therapy embodying features of the presentinvention.

FIG. 2 is an elevated perspective view of an embodiment of a cassettefor controlling fluid flow in the disposable photopheresis kit of FIG.1.

FIG. 3 is an exploded view of the cassette of FIG. 2.

FIG. 4 is a top view of the cassette of FIG. 2 with the cover removedand showing internal tubular circuitry.

FIG. 5 is a bottom view of a cover of cassette of FIG. 2.

FIG. 6 is an elevated perspective view of an embodiment of a filterassembly.

FIG. 7 is bottom perspective view of the filter assembly of FIG. 6.

FIG. 8 is an exploded view of the filter assembly of FIG. 6.

FIG. 9 is a rear perspective view of the filter assembly of FIG. 6.

FIG. 10 is schematic representation of the filter assembly of FIG. 6coupled to pressure sensors and a data processor.

FIG. 11 is a front view of an irradiation chamber.

FIG. 12 is a side longitudinal view of the irradiation chamber of FIG.11.

FIG. 13 is a side transverse view of the irradiation chamber of FIG. 11

FIG. 14 is a cut-away view of a section of the first plate and thesecond plate prior to being joined together to form the irradiationchamber of FIG. 11.

FIG. 15 is a cut-away dimensional end view of the irradiation chamber ofFIG. 11.

FIG. 16 is a perspective view of the irradiation chamber of FIG. 11positioned within a UVA light assembly.

FIG. 17 is an elevated perspective view of an embodiment of a permanenttower system for use in conjunction with a disposable kit forfacilitating a photopheresis therapy session.

FIG. 18 is a cross-sectional view of an embodiment of thephotoactivation chamber, without a UVA light assembly, used in the towersystem of FIG. 17.

FIG. 19 is a cross-sectional view of an embodiment of the centrifugechamber used in the tower system of FIG. 17.

FIG. 20 is an electrical schematic of the leak detection circuitprovided in the photoactivation chamber of FIG. 18.

FIG. 21 is an electrical schematic of the leak detection circuitprovided in the centrifuge chamber of FIG. 19.

FIG. 22 is an elevated perspective view of an embodiment of the fluidflow control deck of the tower system of FIG. 17.

FIG. 23 is a perspective bottom view of the control deck of FIG. 22.

FIG. 24 is an exploded view of the control deck of FIG. 22.

FIG. 25 is a top perspective view of the control deck of FIG. 22 withthe cassette of FIG. 2 loaded thereon.

FIG. 26 is a flowchart of an embodiment of a photopheresis treatmentprocess.

FIG. 27 is a schematic of an embodiment of the fluid flow circuit usedin performing the treatment process of FIG. 26.

FIG. 28 is top perspective view an embodiment of a peristaltic pump.

FIG. 29 is a cross sectional side view of the peristaltic pump of FIG.28.

FIG. 30 is a top perspective view the rotor of the peristaltic pump ofFIG. 29.

FIG. 31 is a bottom perspective view of the rotor of FIG. 30.

FIG. 32 is a top view of the peristaltic pump of FIG. 28.

FIG. 33 is a top view of the peristaltic pump of FIG. 28 in a loadingposition and near the cassette of FIG. 2.

FIG. 34 is an electrical schematic of the infrared communication portcircuit.

FIG. 35 illustrates an embodiment of a centrifuge bowl and a rotatingframe.

FIG. 36 is a dimensional view of the bowl of FIG. 35.

FIG. 37 is an exploded view of the bowl of FIG. 36.

FIG. 38 shows a cross sectional view of the bowl of FIG. 36 along theline XIX-XIX.

FIG. 39A shows a cross sectional view of a connection sleeve in placewith a lumen connector of the bowl of FIG. 38 along the line XX.

FIG. 39B shows another cross sectional view of a connection sleeve inplace with a lumen connector of the bowl of FIG. 38.

FIG. 40 shows a cross sectional view of the top core of the bowl of FIG.37.

FIG. 41 shows a dimensional view of the top core and upper plate of FIG.37.

FIG. 42 shows a bottom view of the top core of FIG. 41.

FIG. 43A shows a dimensional exploded view of the bottom core and alower plate of the bowl of FIG. 37.

FIG. 43B shows an dimensional cross section view of the bottom core anda lower plate of the bowl of FIG. 43A attached together.

FIG. 44 shows an exploded side view of the bottom core and a lower plateof FIG. 43A.

FIG. 45 shows a dimensional view of another embodiment of a conduitassembly.

FIG. 46 shows a dimensional view of the connection sleeve of FIG. 45.

FIG. 47 shows a dimensional view of one end of conduit assembly of FIG.45.

FIG. 48 shows a dimensional view of an anchor end of the presentinvention.

FIG. 49 shows a lateral cross-sectional view of an anchor end.

FIG. 50 shows a horizontal cross-sectional view of an anchor end takenalong line XXI.

FIG. 51 illustrates a dimensional view of the rotating frame of FIG. 35.

FIG. 52 is an enlarged view of a holder for an external conduit.

FIG. 53 shows an alternative embodiment of the bowl with thecross-section taken similarly to that shown in FIG. 38.

FIG. 54 shows an alternative embodiment of the top core.

FIG. 55 shows an alternative embodiment of the connection sleeve.

MODES FOR CARRYING OUT THE INVENTION

Features of the present invention are embodied in the permanent blooddriving equipment, the disposable photopheresis kit, the various deviceswhich make up the disposable kit, and the corresponding treatmentprocess. The following written description is outlined as follows:

I. Disposable Photopheresis Kit

-   -   A. Cassette for Controlling Fluid Flow        -   1. Filter Assembly    -   B. Irradiation Chamber    -   C. Centrifuge Bowl        -   1. Drive Tube

II. Permanent Tower System

-   -   A Photoactivation Chamber    -   B. Centrifuge Chamber    -   C. Fluid Flow Control Deck        -   1. Cassette Clamping Mechanism        -   2. Self-Loading Peristaltic Pumps    -   D. Infra-Red Communication

III. Photopheresis Treatment Process

The above-outline is included to facilitate understanding of thefeatures of the present invention. The outline is not limiting of thepresent invention and is not intended to categorize or limit any aspectof the invention. The inventions are described and illustrated insufficient detail that those skilled in this art can readily make anduse them. However, various alternatives, modifications, and improvementsshould become readily apparent without departing from the spirit andscope of the invention. Specifically, while the invention is describedin the context of a disposable kit and permanent blood drive system foruse in photopheresis therapy, certain aspects of the invention are notso limited and are applicable to kits and systems used for renderingother therapies, such as apheresis or any other extracorporeal bloodtreatment therapy.

I. Disposable Photopheresis Kit

FIG. 1 illustrates disposable photopheresis kit 1000 embodying featuresof the present invention. It is necessary that a new disposable sterilekit be used for each therapy session. In order to facilitate thecirculation of fluids through photopheresis kit 1000, and to treat bloodfluids circulating therethrough, photopheresis kit 1000 is installed inpermanent tower system 2000 (FIG. 17). The installation of photopheresiskit 1000 into tower system 2000 is described in detail below.

Photopheresis kit 1000 comprises cassette 1100, centrifuge bowl 10,irradiation chamber 700, hematocrit sensor 1125, removable data card1195, treatment bag 50, and plasma collection bag 51. Photopheresis kit1000 further comprises saline connector spike 1190 and anticoagulantconnector spike 1191 for respectively connecting saline andanticoagulant fluid bags (not shown). Photopheresis kit 1000 has all thenecessary tubing and connectors to fluidly connect all devices and toroute the circulation of fluids during a photopheresis treatmentsession. All tubing is sterile medical grade flexible tubing. Triportconnectors 1192 are provided at various positions for the introductionof fluids into the tubing if necessary.

Needle adapters 1193 and 1194 are provided for respectively connectingphotopheresis kit 1000 to needles for drawing whole blood from a patientand returning blood fluids to the patient. Alternatively, photopheresiskit 1000 can be adapted to use a single needle to both draw whole bloodfrom the patient and return blood fluids to the patient. However, a twoneedle kit is preferred because of the ability to simultaneously drawwhole blood and return blood fluids to the patient. When a patient ishooked up to photopheresis kit 1000, a closed loop system is formed.

Cassette 1100 acts both as a tube organizer and a fluid flow router.Irradiation chamber 700 is used to expose blood fluids to UV light.Centrifuge bowl 10 separates whole blood into its different componentsaccording to density. Treatment bag 50 is a 1000 mL three port bag.Straight bond port 52 is used to inject a photoactivatable orphotosensitive compound into treatment bag 50. Plasma collection bag 51is 1000 mL two port bag. Both treatment bag 50 and plasma collection bag51 have a hinged cap spike tube 53 which can be used for drainage ifnecessary. Photopheresis kit 1000 further comprises hydrophobic filters1555 and 1556 which are adapted to connect to pressure transducers 1550and 1551 to filter 1500 via vent tubes 1552 and 1553 for monitoring andcontrolling the pressures within tubes connecting the patient (FIG. 10).Monitoring the pressure helps ensure that the kit is operating withinsafe pressure limits. The individual devices of photopheresis kit 1000,and their functioning, are discussed below in detail.

A. Cassette for Controlling Fluid Flow

FIG. 2 shows a top perspective view of a disposable cassette 1100 forvalving, pumping, and controlling the movement of blood fluids during aphotopheresis treatment session. Cassette 1100 has housing 1101 thatforms an internal space that acts as a casing for its various internalcomponents and tubular circuitry. Housing 1101 is preferably made ofhard plastic, but can be made of any suitably rigid material. Housing1101 has side wall 1104 and top surface 1105. Side wall 1104 of housing1101 has tabs 1102 and 1103 extending therefrom. During a photopheresistreatment, cassette 1100 needs to be secured to deck 1200 of towersystem 2000, as is best illustrated in FIG. 25. Tabs 1102 and 1103 helpposition and secure cassette 1100 to deck 1200.

Cassette 1100 has fluid inlet tubes 1106, 1107, 1108, 1109, 1110, 1111,and 1112 for receiving fluids into cassette 1100, fluid outlet tubes1114, 1115, 1116, 1117, 1118, and 1119 for expelling fluids fromcassette 1100, and fluid inlet/outlet tube 1113 that can be used forboth introducing and expelling fluids into and out of cassette 1100.These fluid input and output tubes fluidly couple cassette 1100 to apatient being treated, as well as the various devices of photopheresiskit 1000, such as centrifuge bowl 10, irradiation chamber 700, treatmentbag 50, plasma collection bag 51, and bags containing saline,anticoagulation fluid to form a closed-loop extracorporeal fluid circuit(FIG. 27).

Pump tube loops 1120, 1121, 1122, 1123, and 1124 protrude from side wall1104 of housing 1101. Pump tube loops 1120, 1121, 1122, 1123, and 1124are provided for facilitating the circulation of fluids throughoutphotopheresis kit 1000 during therapy. More specifically, when cassette1100 is secured to deck 1200 for operation, each one of said pump tubeloops 1120, 1121, 1122, 1123, and 1124 are loaded into a correspondingperistaltic pump 1301, 1302, 1303, 1304, and 1305 (FIG. 4). Peristalticpumps 1301, 1302, 1303, 1304, and 1305 drive fluid through therespective pump tube loops 1120, 1121, 1122, 1123, and 1124 in apredetermined direction, thereby driving fluid through photopheresis kit1000 (FIG. 1) as necessary. The operation and automatic loading andunloading of peristaltic pumps 1301, 1302, 1303, 1304, and 1305 isdiscussed in detail below with respect to FIGS. 28-33.

Turning now to FIG. 3, cassette 1100 is shown with housing 1101 in anexploded state. For ease of illustration and description, the internaltubular circuitry within housing 1101 is not illustrated in FIG. 3. Theinternal tubular circuitry is illustrated in FIG. 4 and will bediscussed in relation thereto. Cassette 1100 has filter assembly 1500positioned therein and in fluid connection with inlet tube 1106, outlettube 1114, and one end of each of pump tube loops 1120 and 1121. Filterassembly 1500 comprises vent chambers 1540 and 1542. Filter assembly1500, and its functioning, is discussed in detail below with respect toFIGS. 6-10.

Housing 1101 comprises cover 1130 and base 1131. Cover 1130 has topsurface 1105, a bottom surface 1160 (FIG. 5), and side wall 1104. Cover1130 has openings 1132 and 1133 for allowing vent chambers 1540 and 1542of filter assembly 1500 to extend therethrough. Side wall 1104 has aplurality of tube slots 1134 to allow the inlet tubes, outlet tubes, andpump loop tubes to pass into the internal space of housing 1101 forconnection with the internal tubular circuitry located therein. Only afew tube slots 1134 are labeled in FIG. 3 to avoid numerical crowding.Tabs 1102 and 1103 are positioned on side wall 1104 so as not tointerfere with tube slots 1134. Cover 1130 has occlusion bars 1162 and1162A extending from bottom surface 1160 (FIG. 5). Occlusion bars 1162and 1162A are preferably molded into bottom surface 1160 of cover 1130during its formation.

Base 1131 has a plurality of U-shaped tube-holders 1135 extending upwardfrom top surface 1136. U-shaped tube holders 1135 hold the inlet tubes,outlet tubes, pump loop tubes, filter assembly, and internal tubularcircuitry in place. Only a few U-shaped holders 1135 are labeled in FIG.3 to avoid numerical crowding. Preferably, a U-shaped holder 1135 isprovided on base 1131 at each location where an inlet tube, an outlettube, or a pump loop tube passes through a tube slot 1134 on side wall1104. Male extrusions 1136 protrude from top surface 1136 of base 1131for mating with corresponding female holes 1161 located on bottomsurface 1160 of cover 1130 (FIG. 5). Preferably, a male protrusion 1136is located at or near each of the four corners of base 1130 and nearfilter 1500. Male protrusions 1136 mate with the female holes 1161 toform a snap-fit and secure base 1131 to cover 1130.

Base 1131 further comprises a hub 1140. Hub 1140 is a five-way tubeconnector used to connect five tubes of the internal tubular circuitry.Preferably, three apertures 1137 are located near and surround three ofthe tubes leading into hub 1140. Hub 1140 acts as a centralized junctionwhich can be used, in conjunction with compression actuators 1240-1247(FIG. 22), to direct fluids through photopheresis kit 1000 and to andfrom the patient. In addition to hub 1140, appropriate tube connectors,such as T-connectors 1141 and Y-connector 1142, are used to obtain thedesired flexible tubing pathways.

Five apertures 1137 are located on the floor of base 1130. Each aperture1137 is surrounded by an aperture wall 1138 having slots 1139 forpassing portions of the internal tubular circuitry therethrough. Anelongated aperture 1157 is also provided on the floor of base 1131.Apertures 1137 are located on base 1131 to align with correspondingcompression actuators 1243-1247 of deck 1200 (FIG. 22). Aperture 1157 islocated on base 1131 to align with compression actuators 1240-1242 ofdeck 1200 (FIG. 22). Each aperture 1137 is sized so that a singlecompression actuator 1243-1247 can extend therethrough. Aperture 1157 issized so that three compression actuators 1240-1242 can extendtherethrough. Compression actuators 1240-1247 are used to close/occludeand open certain fluid passageways of the internal tubular circuitry inorder to facilitate or prohibit fluid flow along a desired path. When itis desired to have a certain passageway open so that fluid can flowtherethrough, the compression actuator 1240-1247 for that passageway isin a lowered position However, when it is desired to have a certainfluid passageway closed so that fluid can not flow therethrough, theappropriate compression actuator 1240-1247 is raised, extending thecompression actuator 1240-1247 through aperture 1137 or 1157 andcompressing a portion of the flexible tubular circuitry against bottomsurface 1160 (FIG. 5) of cover 1130, thereby closing that passageway.Preferably, occlusion bars 1163 and 1173 (FIG. 5) are positioned onbottom surface 1160 to align with the compression actuators 1240-1247 sothat the portion of flexible tubing being occluded is compressed againstocclusion bar 1163 or 1173. Alternatively, the occlusion bar can beomitted or located on the compression actuators themselves.

It is preferable for cassette 1100 to have a unique identifier that cancommunicate with and relay information to permanent tower system 2000.The unique identifier is provided to ensure that the disposablephotopheresis kit is compatible with the blood drive equipment intowhich it is being loaded, and that the photopheresis kit is capable ofrunning the desired treatment process. The unique identifier can also beused as a means to ensure that the disposable photopheresis kit is of acertain brand name or make. In the illustrated example, the uniqueidentifier is embodied as data card 1195 (FIG. 2) that is inserted intodata card receiving port 2001 of permanent tower system 2000 (FIG. 17).Data card 1195 has both read and write capabilities and can store datarelating to the treatment therapy performed for future analysis. Theunique identifier can also take on a variety of forms, including, forexample, a microchip that interacts with the blood drive equipment whenthe kit is loaded, a bar code, or a serial number.

Cover 1130 has data card holder 1134 for holding data card 1195 (FIG.1). Data card holder 1134 comprises four elevated ridges in a segmentedrectangular shape for receiving and holding data card 1195 to cassette1100. Data card holder 1134 holds data card 1195 in place via a snap-fit(FIG. 2).

Referring now to FIGS. 1 and 4, the internal tubular circuitry ofcassette 1100 will now be discussed. At least a portion of the internaltubular circuitry is preferably made of flexible plastic tubing that canbe pinched shut by the exertion of pressure without compromising thehermetic integrity of the tube. Base 1131 of cassette 1100 isillustrated in FIG. 4 so that the internal tubular circuitry can beviewed. Inlet tubes 1107 and 1108 and outlet tube 1115 are provided forcoupling cassette 1100 to centrifuge bowl 10 (FIG. 1). Morespecifically, outlet tube 1115 is provide for delivering whole bloodfrom cassette 1100 to centrifuge bowl 10, and inlet tubes 1107 and 1108are respectively provide for returning a lower density blood componentsand higher density blood components to cassette 1100 for further routingthrough photopheresis kit 1000. The lower density blood components caninclude, for example, plasma, leukocytes, platelets, buffy coat, or anycombination thereof. The higher density components can include, forexample, red blood cells. Outlet tube 1117 and inlet tube 1112 fluidlycouple cassette 1100 to irradiation chamber 700. More specifically,outlet tube 1117 is provided for delivering an untreated lower densityblood component, for example buffy coat, to irradiation chamber 700 forexposure to photo energy, while inlet tube 1112 is provided forreturning the treated lower density blood component to cassette 1100 forfurther routing.

Inlet tube 1111 and outlet tube 1116 couple treatment bag 50 to cassette1100. Outlet tube 1116 is provided to deliver an untreated low densityblood component, for example buffy coat, to treatment bag 50. Outlettube 1116 has hematocrit (“HCT”) sensor 1125 operably connected theretoto monitor for the introduction of a high density blood component, suchas red blood cells. HCT sensor 1125 is a photo sensor assembly and isoperably coupled to a controller. HCT sensor 1125 sends a detectionsignal to the controller when red blood cells are detected in outlettube 1116 and the controller will take the appropriate action. Inlettube 1111 is provided to return the untreated low density bloodcomponent from treatment bag 50 to cassette 1100 for further routing.Inlet tubes 1109 and 1110 are respectively connected to a saline andanticoagulant storage bags (not shown) via spikes 1190 and 1191 and areprovided for delivering saline and an anticoagulant fluid to cassette1100 for further routing to the patient.

Inlet/Outlet tube 1113 and outlet tube 1118 couple plasma collection bag50 to cassette 1100. More specifically, outlet tube 1118 delivers ablood component, such as plasma, to plasma collection bag 51.Inlet/Outlet tube 1113 can be used to either deliver red blood cells toplasma collection bag 51 from cassette 1100 or return the bloodcomponent(s) that build up in plasma collection bag 51 to cassette 1100for further routing. Inlet tube 1106 and outlet tubes 1119 and 1114 arecoupled to a patient. Specifically, outlet tube 1114 is provided toreturn treated blood, saline, untreated blood components, treated bloodcomponents, and other fluids back to the patient. Inlet tube 1106 isprovided for delivering untreated whole blood (and a predeterminedamount of an anticoagulant fluid) from the patient to cassette 1100 forrouting and treatment within photopheresis kit 1000. Outlet tube 1119 isspecifically provided for delivering an anticoagulant fluid to inlettube 1106. It is preferable that all tubing is disposable medical gradesterile tubing. Flexible plastic tubing is the most preferred.

Cassette 1100 has five pump tube loops 1120, 1121, 1122, 1123, and 1124for driving blood fluids throughout cassette 1100 and photopheresis kit1000. More specifically, pump tube loop 1121 loads into whole blood pump1301 and respectively drives whole blood in and out of cassette 1100 viainlet tube 1106 and outlet tube 1115, passing through filter 1500 alongthe way. Pump loop tube 1120 loads into return pump 1302 and drivesblood fluids through filter 1500 and back to the patient via outlet tube1114. Pump loop tube 1122 loads into red blood cell pump 1305 and drawsred blood cells from centrifuge bowl 10 and drives them into cassette1100 via inlet line 1108. Pump loop tube 1123 loads into anticoagulantpump 1304 and drives an anticoagulant fluid into cassette 1100 via inlettube 1124 and out of cassette 1100 to via outlet tube 1119, whichconnects with inlet tube 1106. Pump loop tube 1124 loads intorecirculation pump 1303 and drives blood fluids, such as plasma, throughtreatment bag 50 and irradiation chamber 700 from cassette 1100.

Each of peristaltic pumps 1301-1305 are activated when necessary toperform the photopheresis treatment therapy according to an embodimentof the method of the present invention which is described below inrelation to FIGS. 26-27. Peristaltic pumps 1301-1305 can be operated oneat a time or in any combination. The pumps 1301-1305 work in conjunctionwith compression actuators 1240-1247 to direct fluids through desiredpathways of photopheresis kit 1000. Apertures 1137 and 1157 arestrategically located on base 1131 along the internal tubular circuitryto facilitate proper routing. Through the use of compression actuators1240-1247, the fluids can be directed along any pathway or combinationthereof.

1. The Filter Assembly

Filter 1500, which is located within cassette 1100 as described above,is illustrated in detail in FIGS. 6-10. Referring first to FIGS. 6 and7, filter 1500 is illustrated fully assembled. Filter 1500 comprises afilter housing 1501. Filter housing 1501 is preferably constructed of atransparent or translucent medical grade plastic. However, the inventionis not so limited and filter housing 1501 can be constructed of anymaterial that will not contaminate blood or other fluids that areflowing therethrough.

Filter housing 1501 has four fluid connection ports extruding therefrom,namely whole blood inlet port 1502, whole blood outlet port 1503,treated fluid inlet port 1504, and treated fluid outlet port 1505. Ports1502-1505 are standard medical tubing connection ports that allowmedical tubing to be fluidly connected thereto. Ports 1502-1505respectively contain openings 1506, 1507, 1508 and 1509. Openings 1506,1507, 1508 and 1509 extend through ports 1502, 1503, 1504 and 1505,forming fluid passageways into filter housing 1501 at the desiredlocations.

Ports 1502, 1503, 1504 and 1505 are also used to secure filter 1500within cassette 1100. In doing so, ports 1502, 1503, 1504 and 1505 canengage U-shaped fasteners 1135 of cassette 1100 (FIG. 3). Filter housing1501 also has a protrusion 1510 extending the bottom surface of housingfloor 1518. Protrusion 1510 fits into a guide hole of base 1131 ofcassette 1100 (FIG. 3).

Referring now to FIG. 8, filter 1500 is illustrated in an explodedstate. Filter housing 1501 is a two-piece assembly comprising roof 1511and base 1512. Roof 1511 is connected to base 1512 by any means known inthe art, such as ultrasonic welding, heat welding, applying an adhesive,or by designing roof 1511 and base 1512 so that a tight fit resultsbetween the two. While filter housing 1501 is illustrated as a two-pieceassembly, filter housing 1501 can be either a single piece structure ora multi-piece assembly.

Base 1512 has chamber separation wall 1513 extending upward from a topsurface of housing floor 1518 (FIG. 7). When base 1512 and roof 1511 areassembled, top surface 1515 of chamber separation wall 1513 contacts thebottom surface of roof 1511, forming two chambers within the filterhousing, whole blood chamber 1516 and filter chamber 1517. Fluid can notdirectly pass between whole blood chamber 1516 and filter chamber 1517.

Whole blood chamber 1516 is a substantially L-shaped chamber havingfloor 1514. Whole blood chamber 1516 has a whole blood inlet hole 1519and a whole blood outlet hole (not illustrated) in floor 1514. Wholeblood inlet hole 1519 and the whole blood outlet hole are located at ornear the ends of the substantially L-shaped whole blood chamber 1516.Whole blood inlet hole 1519 forms a passageway with opening 1506 ofinlet port 1502 so that a fluid can flow into whole blood chamber 1516.Similarly, the whole blood outlet hole (not illustrated) forms apassageway with opening 1507 of outlet port 1503 so that fluid can flowout of whole blood chamber 1516.

Filter chamber 1517 has floor 1520. Floor 1520 has elevated ridge 1521extending upward therefrom. Elevated ridge 1521 is rectangular and formsa perimeter. While elevated ridge 1521 is rectangular in the illustratedembodiment, elevated ridge 1521 can be any shape so long as it forms anenclosed perimeter. The height of elevated ridge 1521 is less than theheight of chamber separation wall 1513. As such, when roof 1511 and base1512 are assembled, space exists between the top of elevated ridge 1521and the bottom surface of roof 1511. Elevated ridge 1521 and chamberseparation wall 1513 form a trench 1524 there between.

In order to facilitate fluid flow through filter chamber 1517, floor1520 of filter chamber 1517 has treated fluid inlet hole 1522 andtreated fluid outlet hole 1523. Treated fluid inlet hole 1522 is locatedexterior of the perimeter formed by elevated ridge 1521 and forms apassageway with opening 1508 of inlet port 1504 so that a fluid can flowinto filter chamber 1517 from outside filter housing 1501. Treated fluidoutlet hole 1523 is located interior of the perimeter formed by elevatedridge 1521 and forms a passageway with opening 1509 of outlet port 1505so that a fluid can flow out of filter chamber 1517.

Filter 1500 further comprises filter element 1530. Filter element 1530comprises frame 1531 having filter media 1532 positioned therein. Frame1531 has a neck 1534 that forms a filter inlet hole 1533. Filter element1530 is positioned in filter chamber 1517 so that frame 1531 fits intotrench 1524 and neck 1534 surrounds treated blood inlet hole 1522.Filter inlet hole 1533 is aligned with treated fluid inlet hole 1522 sothat incoming fluid can freely flow through holes 1522 and 1533 intofilter chamber 1517. Frame 1531 of filter element 1530 forms a hermeticfit with elevated ridge 1521. All fluid that enters filter chamber 1517through holes 1522 and 1533 must pass through filter media 1532 in orderto exit filter chamber 1517 via treated fluid outlet hole 1523. Filtermedia 1532 preferably has a pore size of approximately 200 microns.Filter media 1532 can be formed of woven mesh, such as woven polyester.

Filter chamber 1517 further comprises filter vent chamber 1540 withinroof 1511. Filter vent chamber 1540 has gas vent 1541 in the form of ahole (FIG. 9). Because gas vent 1541 opens into filter vent chamber 1540which in turn opens into filter chamber 1517, gases that build-up withinfilter chamber 1517 can escape through gas vent 1541. Similarly, wholeblood chamber 1516 comprises blood vent chamber 1542 within roof 1511.Blood vent chamber 1541 has gas vent 1543 in the form of a hole. Becausegas vent 1543 opens into blood vent chamber 1542 which in turn opensinto whole blood chamber 1517, gases that build-up in whole bloodchamber 1516 can escape via gas vent 1543.

FIG. 10 is a top view of filter 1500 having pressure sensors 1550 and1551 connected to gas vents 1541 and 1543. Pressure sensors 1550 and1551 are preferably pressure transducers. Pressure sensor 1550 isconnected to gas vent 1541 via vent tubing 1552. Vent tubing 1552 fitsinto gas vent 1541 so as to form a tight fit and seal. Because gas vent1541 opens into filter vent chamber 1540 which in turn opens into filterchamber 1517, the pressure in vent tubing 1552 is the same as in filterchamber 1517. By measuring the pressure in vent tubing 1552, pressuresensor 1550 also measures the pressure within filter chamber 1517.Similarly, pressure sensor 1551 is connected to gas vent 1543 via venttubing 1553. Vent tubing 1553 fits into gas vent 1543 so as to form atight fit and seal and pressure sensor 1551 measures the pressure withinwhole blood chamber 1516. Filter vent chamber 1540 and blood ventchamber 1542 extend through openings 1132 and 1133 of cassette 1100 whenfilter 1500 is positioned therein (FIG. 2). This allows the pressurewithin chambers 1516 and 1517 to be monitored while still protectingfilter chamber 1500 and the fluid connections thereto.

Pressure sensors 1550 and 1551 are coupled to controller 1554, which isa properly programmed processor. Controller 1554 can be a main processorused to drive the entire system or can be a separate processor coupledto a main processor. Pressure sensors 1550 and 1551 produce electricaloutput signals representative of the pressure readings within chambers1517 and 1516 respectively. Controller 1554 receives on a frequent orcontinuous basis data representing the pressure within chambers 1516 and1517. Controller 1554 is programmed with values representing desiredpressures within chambers 1516 and 1517. Controller 1554 continuouslyanalyzes the pressure data it receives from pressure sensors 1550 and1551 to determine whether the pressure readings are within apredetermined range from the desired pressure for chambers 1517 and1516. Controller 1554 is also coupled to whole blood pump 1301 andreturn pump 1302. In response to the pressure data received frompressure sensors 1551 and 1550, controller 1554 is programmed to controlthe speed of whole blood pump 1301 and return pump 1302, therebyadjusting the flow rates through the pumps 1301 and 1301. Adjustingthese flow rates in turn adjust the pressure within whole blood chambers1516 and filter chamber 1517 respectively. It is in this way that thepressure within the lines drawing and returning blood to and from thepatient is maintained at acceptable levels.

The functioning of filter 1500 during a photopheresis therapy sessionwill now be discussed in relation to FIGS. 1, 6, and 10. While thefunctioning of filter 1500 will be described in detail with respect todrawing whole blood from a patient and returning a component of saidwhole blood back into the patient after it is treated, the invention isnot so limited. Filter 1500 can be used in connection with almost anyfluid, including red blood cells, white blood cells, buffy coat, plasma,or a combination thereof.

Whole blood pump 1601 draws whole blood from a patient who is connectedto photopheresis kit 1000 via a needle connected to port 1193. Therotational speed of whole blood pump is set so that the pressure of theline drawing the whole blood from the patient is at an acceptable level.Upon being drawn from the patient, the whole blood passes into cassette1100 via inlet tube 1106. Inlet tube 1106 is fluidly connected to inletport 1502 of filter 1500. The whole blood passes through opening 1506 ofinlet port 1502 and into L-shaped whole blood chamber 1516. The wholeblood enters chamber 1516 through inlet hole 1519 which is located onfloor 1514. As more whole blood enters chamber 1516, the whole bloodspills along floor 1514 until it reaches the whole blood outlet hole(not illustrated) at the other end of L-shaped whole blood chamber 1516.As discussed above, the whole blood outlet whole forms a passageway withopening 1507 of outlet port 1503. The whole blood that is within chamber1516 flows across floor 1514, through the whole blood outlet hole, intooutlet port 1503, and out of filter 1500 through opening 1507.

As the whole blood passes through whole blood chamber 1516, gases thatare trapped in the whole blood escape. These gases collect in blood ventchamber 1542 and then escape via gas vent 1543. Pressure sensor 1551continuously monitors the pressure within blood chamber 1516 throughvent tube 1553 and transmits corresponding pressure data to controller1554. Controller 1554 analyzes the received pressure data and ifnecessary adjusts the speed of whole blood pump 1301, thereby adjustingthe flow rate and pressure within chamber 1516 and inlet tube 1106.Controller 1554 adjust the pump speed to ensure that the pressure iswithin the desired pressure range.

The whole blood then exits filter 1500 through outlet port 1503 andpasses out of cassette 1100 via outlet tube 1115. The whole blood isthen separated into components and/or treated as described in detailbelow. Before being returned to the patient, this treated fluid (i.e.treated blood or blood components) must be filtered. Untreated fluidssuch as red blood cells also must be filtered and will subjected to thebelow filtering process. The treated fluid is fed into filter chamber1517 through opening 1508 of inlet port 1504. Inlet port 1504 is fluidlyconnected to pump loop tube 1120. The treated fluid enters filterchamber 1517 through inlet hole 1522 and passes through filter inlethole 1533 of filter element 1530. The treated fluid fills filter chamber1517 until it spills over frame 1531 of filter element 1530, which issecured to elevated ridge 1521. The treated fluid passes through filtermedia 1532. Filter media 1532 removes contaminants and other undesiredmaterials from the treated fluid while at the same facilitating therelease of trapped gases from the treated fluid. The treated fluid thatpasses through filter media 1532 gathers on floor 1520 of filter chamber1517 within the perimeter formed by elevated ridge 1521. This treatedfluid then passes into treated fluid outlet hole 1523 and out of filter1500 through opening 1506 of outlet port 1502. The treated fluid is thenreturned to the patient via outlet tube 1114, which is fluidly connectedto outlet port 1502. The treated fluid is driven through filter chamber1517 and outlet tube 1114 by return pump 1302.

Gases that are trapped in the treated fluid escape and collect in filtervent chamber 1540 as the treated fluid flows through filter chamber1517. These gases then escape filter 1500 via gas vent 1541. Pressuresensor 1550 continuously monitors the pressure within filter chamber1517 through vent tube 1552 and transmits corresponding pressure data tocontroller 1554. Controller 1554 analyzes the received pressure data andcompares it to the desired pressure value and range. If necessary,controller 1554 adjusts the speed of return pump 1302, thereby adjustingthe flow rate and pressure within chamber 1517 and outlet tube 1114.

B. Irradiation Chamber

FIGS. 11-16 illustrate irradiation chamber 700 of photopheresis kit 1000in detail. Referring first to FIG. 11, irradiation chamber 700 is formedby joining two plates, a front and a back plate having a thickness ofpreferably about 0.06 in. to about 0.2 in., which are preferablycomprised of a material ideally transparent to the wavelength ofelectromagnetic radiation. In the case of ultraviolet A radiation,polycarbonate has been found most preferred although other materialssuch as acrylic may be employed. Similarly, many known methods ofbonding may be employed and need not be expanded on here.

The first plate 702 has a first surface 712 and a second surface 714. Ina preferred embodiment the first plate 702 has a first port 705 on afirst surface 712, in fluid communications with the second surface 714.The second surface 714 of the first plate 702 has a raised boundary 726Adefining an enclosure. The boundary 726A preferably extendssubstantially perpendicular from the second surface 714 (i.e. about80-100 degrees). Extending from the second surface 714 (preferablysubstantially perpendicularly) are raised partitions 720A. The boundary726A surrounds the partitions 720A. One end of each partition 720Aextends and contacts the boundary 726A.

The second plate 701 has a first surface 711 and a second surface 713.In a preferred embodiment the second plate 701 preferably has a secondport 730 on a first surface 711, in fluid communications with the secondsurface 713. The second surface 713 of the back plate 701 has a raisedboundary 726B defining an enclosure. The boundary 726B preferablyextends substantially perpendicular from the second surface 713 (i.e.about 80-100 degrees). Extending from the second surface 713 (preferablysubstantially perpendicular) are raised partitions (720B). The boundary726B surrounds the partitions 720B. One end of each partition 720Aextends and contacts one side of boundary (726B).

The joining of the second surfaces of the first and second platesresults in a fluid tight junction between boundaries 726A and 726Bthereby forming boundary 726. Partitions 720A and 720B are also joinedforming a fluid tight junction thereby forming partition 720. Theboundary 726 forms an irradiation chamber 700 and together with thepartitions 720 provides a pathway 710 having channels 715 for conductingfluid. The pathway maybe serpentine, zig-zag, or dove-tailed. Currentlypreferred is a serpentine pathway.

With reference to FIGS. 11 and 12, irradiation chamber 700 comprises aserpentine pathway 710 for conducting patient fluid, such as buffy coator white blood cells, from inlet port 705 to outlet port 730, i.e., theserpentine pathway 710 is in fluid communication with inlet port 705 offront plate 702 and outlet port 730 of back plate 701. Patient fluid issupplied from cassette 1100 to inlet port 705 via outlet tube 1117.After photoactivation and passing through serpentine pathway 710, thetreated patient fluid is returned to cassette 1100 via inlet tube 1112(FIGS. 1 and 4). The patient fluid is driven by recirculation pump 1303.Self-shielding effects of the cells is reduced while the cells arephotoactivated by irradiation impinging upon both sides of irradiationchamber 700.

FIG. 11 shows pin 740 and recess 735 which align the two plates ofirradiation chamber prior to being joined together in a sealingarrangement by RF welding, heat impulse welding, solvent welding oradhesive bonding. Joining of the plates by adhesive bonding and RFwelding is more preferred. Joining of the front and back plates by RFwelding is most preferred as the design of the raised partitions 720 andperimeter 725 minimizes flashing and allows for even application of RFenergy. Locations of pin 740 and recess 735 may be inside serpentinepathway 710 or outside of serpentine pathway 710. FIG. 2 also shows aview of an irradiation chamber with axis L. Rotation of chamber 700 180degree about axis L gives the original configuration of the irradiationchamber. The irradiation chamber of the present invention has C₂symmetry about axis L.

Referring to FIGS. 11, 13, and 16, the leukocyte enriched blood, plasma,and priming solution are delivered through inlet port 705 of front plate702 of irradiation chamber 700 into channel 715. The channel 715 in theirradiation chamber 700 is relatively “thin” (e.g. on the order ofapproximately 0.04″ as distance between two plates) in order to presentlarge surface area of leukocyte rich blood to irradiation and reduce theself-shielding effects encountered with lower surface area/volumeratios. The cross section shape of channel 715 is substantiallyrectangular (e.g. rectangular, rhomboidal or trapezoidal) which has asits long side the distance between partition 720 and the distancebetween the plates as its short side. The shape of the cross section isdesigned for optimal irradiation of cells passing through channel 715.While a serpentine pathway 710 is preferred in order to avoid orminimize stagnant areas of flow, other arrangements are contemplated.

The irradiation chamber 700 allows efficient activation ofphotoactivatable agents by irradiation from a light array assembly, suchas the PHOTOSETTE®'s two banks of UVA lamps (758) for activation (FIG.16). The irradiation plate and UVA light assembly (759) are designed tobe used in a setting where edge 706 is oriented downward and edge 707points upward. In this orientation, fluids entering input port 705 canexit from outlet port 730 with the aid of gravity. In the most preferredembodiment, irradiation of both sides of the irradiation chamber takesplace concurrently while still permitting facile removal of the chamber.UVA light assembly 759 is located within UV chamber 750 of permanenttower system 2000 (FIGS. 17 and 18).

The irradiation chamber's fluid pathway loops to form two or morechannels in which the leukocyte-enriched blood is circulated duringphotoactivation by UVA light. Preferably, irradiation chamber 700 hasbetween 4 to 12 channels. More preferably, the irradiation chamber has 6to 8 channels. Most preferably, the irradiation chamber has 8 channels.

FIG. 14 shows cut-away views of the irradiation chamber. The channels715 of serpentine pathway 710 are formed by the joining of raisedpartition 720 and perimeter 726 of the plates.

The irradiation chamber of the present invention can be made from abiocompatible material and can be sterilized by known methods such asheating, radiation exposure or treatment with ethylene oxide (ETO).

The method of irradiating cells using irradiation chamber 700 duringextracorporeal treatment of cells with electromagnetic radiation (UVA)to be used in the treatment of a patient (such as to induce apoptosis inthe cells and administer the cells into the patient) will now bediscussed. Preferably the cells treated will be white cells.

In one embodiment of this method, a photoactivatable or photosensitivecompound is first administered to at least a portion of the blood of arecipient prior to the extracorporeal treatment of the cells. Thephotoactivatable or photosensitive compound may be administered in vivo(e.g., orally or intravenously). The photosensitive compound, whenadministered in vivo may be administered orally, but also may beadministered intravenously and/or by other conventional administrationroutes. The oral dosage of the photosensitive compound may be in therange of about 0.3 to about 0.7 mg/kg., more specifically, about 0.6mg/kg.

When administered orally, the photosensitive compound may beadministered at least about one hour prior to the photopheresistreatment and no more than about three hours prior to the photopheresistreatment. If administered intravenously, the times would be shorter.Alternatively, the photosensitive compound may be administered prior toor contemporaneously with exposure to ultraviolet light. Thephotosensitive compound may be administered to whole blood or a fractionthereof provided that the target blood cells or blood components receivethe photosensitive compound. A portion of the blood could first beprocessed using known methods to substantially remove the erythrocytesand the photoactive compound may then be administered to the resultingenriched leukocyte fraction. In one embodiment, the blood cells comprisewhite blood cells, specifically, T-cells.

The photoactivatable or photosensitive compound may, in the case of somepsoralens, be capable of binding to nucleic acids upon activation byexposure to electromagnetic radiation of a prescribed spectrum, e.g.,ultraviolet light.

Photoactive compounds may include, but are not limited to, compoundsknown as psoralens (or furocoumarins) as well as psoralen derivativessuch as those described in, for example, U.S. Pat. No. 4,321,919 andU.S. Pat. No. 5,399,719. The photoactivatable or photosensitivecompounds that may be used in accordance with the present inventioninclude, but are not limited to, psoralen and psoralen derivatives;8-methoxypsoralen; 4,5′8-trimethylpsoralen; 5-methoxypsoralen;4-methylpsoralen; 4,4-dimethylpsoralen; 4-5′-dimethylpsoralen;4′-aminomethyl-4,5′,8-trimethylpsoralen;4′-hydroxymethyl-4,5′,8-trimethylpsoralen; 4′,8-methoxypsoralen; and a4′-(omega-amino-2-oxa) alkyl-4,5′,8-trimethylpsoralen, including but notlimited to 4′-(4-amino-2-oxa)butyl-4,5′,8-trimethylpsoralen. In oneembodiment, the photosensitive compound that may be used comprises thepsoralen derivative, amotosalen (S-59) (Cerus, Corp., Concord, Calif.).See, e.g., U.S. Pat. Nos. 6,552,286; 6,469,052; and 6,420,570. Inanother embodiment, the photosensitive compound that may be used inaccordance with the invention comprises 8-methoxypsoralen.

Methoxsalen is a naturally occurring photoactive substance found in theseed of the Ammi majus (umbelliferae plant). It belongs to a class ofcompounds known as psoralens or furocoumarins. The chemical name is9-methoxy-7H-furo[3,2-g][1]-benzopyran-7-one. The formulation of thedrug is a sterile liquid at a concentration of 20 mcg/mL in a 10 mLvial. See http://www.therakos.com/TherakosUS/pdf/uvadexpi.pdf.Toxicology studies of extracorporeal photopheresis and different dosagesof UVADEX® and ultraviolet light in beagle dogs is located in theinvestigator's brochure.

Next, the portion of the subject's blood, recipient's blood, or thedonor's blood to which the photoactive compound has been administered istreated by subjecting the portion of the blood to photopheresis usingultraviolet light. The photopheresis treatment may be carried out usinglong wavelength ultraviolet light (UVA) at a wavelength within the rangeof 320 to 400 nm. Such a range is not limiting, however, but is merelyprovided as an example. The exposure to ultraviolet light during thephotopheresis treatment may have a duration of sufficient length todeliver, for example, about 1-2 J/cm² to the blood.

The photopheresis step is carried out in vitro by installing irradiationchamber 700 into photoactivation chamber 750 of permanent tower system2000 (FIGS. 17 and 18). In one embodiment, when the photopheresis stepis carried out in vitro, at least a fraction of the treated blood isreturned to the subject, recipient, or donor. The treated blood or thetreated enriched leukocyte fraction (as the case may be) may then beadministered back to the subject, recipient, or donor.

The photopheresis process consists of three phases including: 1) thecollection of a buffy-coat fraction (leukocyte-enriched), 2) irradiationof the collected buffy coat fraction, and 3) reinfusion of the treatedwhite blood cells. This process will be discussed below in greaterdetail. Generally, whole blood is centrifuged and separated incentrifuge bowl 10. A total of approximately 240 ml of buffy coat and300 ml of plasma are separated and saved for UVA irradiation.

The collected plasma and buffy coat are mixed with heparinized normalsaline and UVADEX®. (water soluble 8-methoxypsoralin). This mixtureflows in a 1.4 mm thick layer through the irradiation chamber of thepresent invention. The irradiation chamber 700, is inserted inphotoactivation chamber 750 of tower system 2000 between two banks ofUVA lamps of the PHOTOSETTE® (FIG. 15). PHOTOSETTE® UVA lamps irradiateboth sides of this UVA-transparent irradiation chamber 700, permittingexposure to ultraviolet A light, yielding an average exposure perlymphocyte of 1-2 J/cm². Following the photoactivation period, the cellsare removed from the irradiation chamber 700.

In a preferred embodiment of the present invention the cells are removedby the action of gravity and any cells remaining in the chamber aredisplaced from the chamber with additional fluid selected from the groupconsisting of saline, plasma, and combinations thereof. For patients whoare small such as children (e.g. under 30 kg) or patients whose vascularsystem is easily overloaded with fluids the amount of additional fluidused to was the irradiation chamber will preferably be not more than 2×the volume of the chamber, preferably not more than 1× the volume of thechamber, more preferably not more than 0.5× the volume of the chamber0.25× the volume of the chamber. The treated cells volume is reinfusedto the patient.

For a description of similar photopheresis systems and methods, see U.S.patent application Ser. No. 09/480,893, which is expressly incorporatedherein by reference. Also useful herein are the methods and systemsdescribed in U.S. Pat. Nos. 5,951,509; 5,985,914; 5,984,887, 4,464,166;4,428,744; 4,398,906; 4,321,919; PCT Publication Nos. WO 97/36634; andWO 97/36581, all of which are entirely expressly incorporated herein byreference.

The effective amount of light energy that is delivered to the biologicalfluids may be determined using the methods and systems described in U.S.Pat. No. 6,219,584, which is entirely expressly incorporated herein byreference. Indeed, the application of ECP to the various diseasesdescribed herein may require an adjustment of the amount of light energyto optimize the treatment process.

Furthermore, the photosensitizing agent used in the ECP process may beremoved prior to returning the treated biological fluid to the patient.For example, Methoxsalen (UVADEX®) is utilized in the ECP process.Methoxsalen belong to a group of compounds known as psoralens. Theexposure to methoxsalen or other psoralens may cause undesirable effectson the subject, recipient, or donor such as phototoxicity or other toxiceffects associated with psoralen and their decomposition products.Therefore, the psoralen, psoralen derivatives, or psoralen decompositionproducts that may remain in the biological fluid may be removed after UVexposure. A process for the removal of psoralen biological fluids isdescribed in U.S. Pat. No. 6,228,995, which is entirely expresslyincorporated herein by reference.

C. Centrifuge Bowl

In a specific embodiment, the present invention relates to methods andapparatus that separate fluid components, such as, for example, thecomponents of a biological fluid by density or weight. Biological fluidsencompass fluids that comprise, exist in, or are used in, or deliveredto living organisms. Indeed, biological fluids may comprise bodilyfluids and their components, such as blood cells, plasma, and otherfluids that comprise biological components, including living organismssuch as bacteria, cells, or other cellular components. Biological fluidsmay also comprise whole blood or specific whole blood components,including red blood cells, platelets, white blood cells, and precursorcells. In particular, it may be desirable to remove blood from a patientfor treatment, such as for example, extracorporeal treatment. It is tobe understood, however, that the present invention is adaptable to usewith various centrifugal processing apparatus, and the specific examplegiven herein is merely for illustrative purposes. Other uses for theseparation techniques and apparatus may include other medical processessuch as dialysis, chemotherapy, platelet separation and removal, andseparation and removal of other specific cells. Additionally, thepresent invention may be used to separate other types of fluids thatinclude a wide variety of non-medical uses, such as, for example, oiland fluid component separation. All components used in the presentinvention should not adversely affect biological fluids or render themunsuitable for their intended uses, such as those described herein andmay be made of any suitable material compatible with uses describedherein including, but not limited to plastics, such as polycarbonate,methyl methacrylate, styrene-acrylonitrile, acrylic, styrene,acrylonitrile or any other plastic. Where parts of the present inventionare indicated to be attached together and form a fluid tight seal anyappropriate conventional means of joining the parts may be usedincluding but not limited to, adhesives, ultrasonic welding or RFwelding.

The present invention has several advantages over centrifuges what useconventional Latham bowl. The Latham bowl in the UVAR® XTS™ system hasone inlet port that allows whole blood to come into the bowl and oneoutlet port that allows plasma and buffy coat to come out. Having onlytwo ports limits the volume of buffy coat that can be collected percycle. Each cycle involves filling the bowl with whole blood; 2)spinning the bowl to separate whole blood into plasma, buffy coat, andred blood cells; 3) collecting buffy coat for treatment, 4) bringing thebowl to rest; and 5) returning collected plasma and red blood cells.This buffy coat collection method may be characterized as being“batch-like” as the volume of buffy coat required for irradiationtreatment can only be collected after several cycles of buffy coatcollection. The limited volume of collected buffy coat per cycle resultsfrom the accumulated red blood cells remained inside the bowl. Thus theaccumulated red blood cells that can only be emptied at the end of abuffy coat collection cycle is an inherent limitation of the LathamBowl.

The bowl of the instant invention has three separate fluid conduits thatcan be used as an inlet port and two outlet ports. The additional fluidconduits allows for 1) reduce patient treatment time by havingcontinuous spinning during the entire buffy coat collection processwithout having to stop spinning the bowl for removal of accumulated redblood cells; 2) treat small blood volume patients; by having collectedred blood cells returned to patients continuously, these patients may bemore amenable to medical treatments requiring the use of the buffy coator fractions thereof such as extracorporeal photopheresis; 3) betterseparation of different components of fractions of cells within thebuffy coat due to the increased spinning or rotation time and 4) theability to separate high density red blood cells fractions from wholeblood. This centrifuge bowl also provides the opportunity for reducedtreatment time for any medical procedure requiring buffy coat fractionsto be collected from patients that are substantially free of red bloodcells, such as extra corporeal photopheresis.

To achieve the objects in accordance with the purpose of the presentinvention, as embodied and broadly described herein, FIGS. 35 and 36depict specific embodiments of the present invention. The embodimentdepicted in FIG. 35 comprises a centrifuge bowl 10A, conduit assembly860A, frame 910A and stationary restraint 918A. The centrifuge bowl 10Ais in fluid communications with external conduit 20A of conduit assembly860A. Lower sleeve end 832A (FIG. 46) of connection sleeve 500A issecured to bowl 10A. Upper sleeve end 831A of connection sleeve 500A issecured to external conduit 20A, connecting the external conduit 20A tobowl 10A and providing fluid communications from external conduit 20A tobowl 10A. The fluid communications enables fluid 800 to be suppliedthrough external conduit 20A to the bowl 10A. Similarly this fluidcommunications also enables separated fluid components 810 and 820 to beremoved from bowl 10A through external conduit 20A. Bowl 10A and frame910A are adapted to be rotated around center axis 11A.

Referring to FIG. 36, bowl 10A comprises outer housing 100A, connectionsleeve 500A, top core 200A, bottom core 201A, and housing floor 180A.Outer housing 100A may be constructed of any suitable biocompatiblematerial as previously described for the purpose of the illustration inFIG. 36 the outer housing 100A is constructed of clear plastic so thatcores 200A and 201A are visible there through. Outer housing 100A isattached to a housing floor 180A, which in turn comprises protrusions150A for locking bowl 10A into a rotational device such as rotationaldevice 900A. Bowl 10A is preferably simplified in construction and iseasy to manufacture by molding or other known manufacturing processes,such that it may be disposable or used for a limited number oftreatments, and is most preferably capable of containing about 125 ml offluid, such fluid possibly being pressurized. In alternativeembodiments, the volume capacity of the bowl may vary depending upon thehealth of the patient and his or her allowable extracorporeal volume.The volume capacity of the bowl may also vary depending upon the use ofthe bowl or the particular treatment for which the bowl is utilized.Additionally, to avoid contamination of biological fluids, or exposureof persons involved in the processing operation to the fluids, thetransfer operations are preferably carried out within a sealed flowsystem, possibly pressurized, preferably formed of flexible plastic orsimilar material which can be disposed of after each use.

As is illustrated in FIGS. 36 and 37, the outer housing 100A issubstantially conical having an upper housing end 110A, an outer housingwall 120A and a lower housing end 190A. Outer housing 100A may be madeof plastic (such as those plastics listed previously), or any othersuitable material. Upper housing end 110A has an outer surface 110B,inner surface 110C and housing outlet 700A providing a passage betweensaid surfaces. Preferably the upper housing will also have a neck 115Aformed about the housing outlet 700A. The housing outlet 700A and neck115A are sized to allow body 830A of the connection sleeve 500A to passthrough while retaining sleeve flange 790A, which extends from the body830A of connection sleeve 500A. In one embodiment of the presentinvention an o-ring 791A may be inserted between the sleeve flange 790Aand inner surface 110C of the housing end 110A to ensure a fluid tightseal is provided. In an alternative embodiment of the present inventionillustrated in FIG. 53, a second sleeve flange 790B extends from thebody 830A of connection sleeve 500B distal to the sleeve flange 790A.Both sleeve flange 790A and 790B being adapted to fit within neck 115Aand retain o-ring 791A therebetween. A fluid tight seal is provided inthis embodiment by the o-ring contacting body 830A and inner surface110C of the housing end 110A adjacent to the neck 115A. However,connection sleeve 500A can be secured to bowl 10A by any suitable means,including for example, a lip, groove, or tight fit and adhesive with acomponent of bowl 10A. The outer housing wall joins the upper housingend 110A and lower housing end 190A. Lower housing end 190A is attachedto a housing floor 180A of greater diameter than upper end 110A. Housingfloor 180A is adapted to mate with the lower housing end 190A andprovide a fluid tight seal therewith. Any conventional means may be usedto secure the lower housing end 190A to the housing floor 180A,including but not limited to, adhesives, ultrasonic welding or RFwelding. Housing floor 180A may have an indentation 185A that is used tocollect denser fluid 810. The diameter of outer housing 100A increasesfrom upper housing end 110A to lower housing end 190A.

Outer housing 100A is adapted to rotatably connect to a rotationaldevice 900 (FIG. 35), such as for example, a rotor drive system or arotating bracket 910. The rotatable connection may, for example, be abearing that allows free rotation of bowl 10A. Outer housing 100Apreferably has a locking mechanism. The locking mechanism may be one ormore protrusions 150A designed to interact with correspondingindentations in a centrifuge container or any other suitableinterconnect or locking mechanism or equivalent known in the art. Thelocking mechanism may also comprise a key slot 160 (FIG. 51).

Referring to FIG. 37, outer housing 100A and the base 180A define aninterior volume 710A in which cores 200A and 201A will fit when bowl 10Ais assembled. When fully assembled, cores 200A and 201A are fully withininterior volume 710A of outer housing 100A, occupying a coaxial volumeof interior volume 710A about axis 11A.

Referring to FIGS. 38, 40 and 44, the top core 200A and bottom core 201Aare substantially conical and respectively have upper core ends 205A,206A; outer core walls 210A, 211A; and lower core ends 295A, 296A. Thecores 200A, 201A occupy coaxial volumes of interior volume 710A of bowl10A and forming separation volume 220A between upper end 205A and outerwall 210A of top core 200A and outer wall 211A and lower core end 296Aof bottom core 201A and outer housing 100A. Separation volume 220A isthat space of interior volume 710A that is between cores 200A and 201Aand outer housing 100A.

As depicted in FIGS. 40 and 41 top core 200A comprises upper core end205A and a lower core end 295A that are joined by outer core wall 210A.The outer core wall 210A having an outer surface 210B and inner wallsurface 210C and a lower edge 210D. The diameter of top core 200Apreferably increases from upper core end 205A to lower core end 295A.Upper core end 205A also comprises an outer surface 205B and an innersurface 205C. Centrally located about center axis and extendingperpendicularly from the upper surface 205B is lumen connector 481A.Lumen connector 481A has a top surface 482A and a wall surface 482B. Topsurface 482A has two passages 303B and 325D that provide fluidcommunications through the upper core end 205A with second bowl channel410A and first bowl channel 420A respectively. Second bowl channel 410Ais a conduit that has a conduit wall 325A that extends perpendicularlyfrom the inner surface 481C of lumen connector 481A.

As shown on FIGS. 39B, 39A and 40, second bowl channel 410 has fluidcommunication with conduit channel 760A through conduit 321A having afirst end 321B and a second end 321C that is adapted to fit into passage325D of lumen connector 481A. In operation conduit channel 760A ofexternal conduit 20A has fluid communication with bowl channel 410A.First bowl channel 420A is a second conduit that has a channel wall 401Athat extends substantially perpendicularly from inner surface 481C ofthe lumen connector 481A. As shown in FIGS. 39A, 39B and 40, first bowlchannel 420A has fluid communication with conduit channel 780A ofexternal conduit 20A through hollow cylinder 322A having a first end322B and a second end 322C adapted to fit opening 303B top surface 482A.As is illustrated in one embodiment of the present invention, secondbowl channel 410A is disposed within first bowl channel 420A. In analternative embodiment of the present invention illustrated in FIG. 53,conduit wall 325A may be composed of upper part 325F and lower part 325Gand be fused with channel walls 401A and 402A.

Top surface 482A also has indentation 483A which provides fluidcommunications with chamber 740A. When assembled, chamber 740A isdefined by lumen mounting recess 851A less the volumes occupied byhollow cylinders 321A and 322A in the connection junction of connectionsleeve 500A and lumen connector 481A. Chamber 740A has fluidcommunication with conduit channel 770A and with separation volume 220Anear neck 115A through indentation 483A. Thus indentation 483A forms apassageway for the removal of second separated fluid component 820through bowl chamber 740A. Optionally present on the outer surface 205Bare a plurality of spacers 207A which extend from the outer surface andcontact the inner surface 110C of the upper housing end 110A to ensurefluid communications between the separation volume 220A and thepassageway formed by the indentations 483A.

In an alternative embodiment illustrated in FIGS. 53, 54 and 55,conduits 321A and 322A may be affixed to openings 325D and 303B in thetop surface 482A of the lumen connector 481A. Additionally, indentations483A may form a plurality channels in the lumen connector 481A and beadapted to form chamber 740B when connected to connection sleeve 500A or500B. Chamber 740B is adapted to have one or more surfaces 742A that canmate with the male end 853A of the connection sleeve 500A (male end 853Asurrounds end 861 of external conduit 20A). To facilitate the correctorientation of the connection sleeve 500A to the lumen connector 481Athe shape of the male end 853A and chamber 740B may be nonsymmetrical oras is illustrated in FIGS. 53, 54 and 55 a guide 855A may be providedwhich extends from the top surface of the lumen connector 481A and isadapted to fit within opening 857A of the sleeve flange 790A.

Referring back to FIG. 40, the lower core end 295A comprises an upperplate 299A having a top surface 298A, a bottom surface 297A, and an edge299B that attaches and makes direct contact with lower edge 210D of theouter core wall 210A. The edge 299B of the upper plate 299A is adaptedto be joined with lower edge 210D of outer core wall 210A and form afluid tight seal therewith. Extending perpendicularly from the topsurface 298A of upper plate 299A is a channel wall 402A, having an upperend 402B and a lower end 402C and surrounds opening 303A which issubstantially in the center of upper plate 299A. A number of fins 403A,attached to the outside surface of channel wall 402A and top surface298A, supports lumen wall 402A. The channel wall 402A is adapted to matewith channel wall 401A forming a fluid tight seal and providing lumen400A. First bowl channel 420A is in fluid communications with conduitchannel 780A of external conduit 20A through conduit 322A. Opening 303Aprovides fluid communications from lumen 400A to separation volume 220Aas will be further discussed. First bowl channel 420A also surroundssecond bowl channel 410A.

Referring to FIGS. 43A, 43B and 44, bottom core 201A comprises an uppercore end 206A, a outer core wall 211A and a lower core end 296A. Theouter core wall 211A having an outer surface 211B, an inner wall 211Cand lower edge 211D. The diameter of bottom core 201A preferablyincreases from upper core end 206A to lower core end 296A. Bottom core201A also has a top surface 309A and a bottom surface 309B. Top surface309A has an indentation 186A (preferably generally circular) substantialin the center of the surface 309A of the upper core end 206A. Theindentation 186A has an upper surface 186B and an inner surface 186C.The upper surface 186B of the indentation 186A has therein an opening324D which extends through to the inner surface 186C. In an alternativeembodiment of the present invention illustrated in FIG. 53, the uppersurface 186B, may also have a recess a 186D adapted to receive an o-ringand form a fluid type seal around the lower end of 325B of conduit wall325A. Extending perpendicularly from inner surface 186C around saidopening 324D is conduit wall 324A having a distal end 324B. On the topsurface 309A extending from the indentation 186A to the outer surface211B of the outer core wall 211A are one or more channels 305A. The topsurface 309A may be horizontal or slope upward or downward fromindentation 186A. If top surface 309A slopes upward or downward fromindentation 186A to core end 206A, one skilled in the art would be ableto adjust the shapes of upper plate 299A and upper core end 295Aaccordingly. Channels 305A may have an even depth through out the lengthof the channel 305A. However, channel 305A may slope downward or upwardradially from the center. One skilled in the art would see that if topsurface 309A slopes upward or downward and channel 305A has a constantdepth, then channel 305A slopes upward or downward accordingly.

Referring to FIG. 38, the bottom surface 297A of upper plate 299A is indirect contact with the top surface area 309A of bottom core 201A whencompletely assembled. This contact forms a fluid tight seal between thetwo surface areas forming an opening 305B from the indentation 186A tochannel 305A. A second opening 305C from channel 305A is formed in theouter surface 211B of outer core wall 211A. The opening 305B providesfluid communications from indentation 186A through channel 305A andopening 305C to separation volume 220A (FIGS. 38 and 40). Thus fluid 800flows through conduit channel 780A and subsequently passes through firstbowl channel 420A. From first bowl channel 420A, fluid 800 then goes tothrough channel 305A to the separation volume 220A.

Referring to FIGS. 43A and 44, the lower core end 296A has a lower plate300A, which has a top surface 300B, a bottom surface 300C and outer edge300D. Extending from the bottom surface 300C of the lower plate 300 areone or more protrusions 301A. The outer edge 300D is adapted to beattached to the lower edge 211D of the outer core wall 211A and providea fluid tight seal therewith. Positioned above housing floor 180A, lowerplate 300A is circular and curves upward radially from its center(illustrated in FIG. 44). Alternatively, lower plate 300A can be flat.As shown in FIG. 38 when positioned above housing floor 180A, a volume220C exists between lower plate 300A and housing floor 180A. This volume220C is in fluid communication with separation volume 220A. Lower plate300A may be made of plastic or any other suitable material.Additionally, extending substantially perpendicularly from the lowersurface 300C of lower plate 300A is a conduit 320A. Conduit 320A has afirst end 320B that extends into the space 220C between lower plate 300Aand housing floor 180A and a second end 320C that extends above the topsurface 300B of lower plate 300A. The diameter of conduit 320A isadapted to have a tight fit with conduit wall end 324B. The volumeinside conduit walls 324A and 325A comprises a lumen 400B. The volumedefined by lower plate 300A, inner surface 211C, and ceiling 253A ofbottom core 201A, excluding second bowl channel 410A, may comprise ofair or a solid material (See FIGS. 43B and 44).

In an alternative embodiment of the present invention as illustrated inFIG. 53, support walls 405A and 407A may be optionally present. Supportwall 405A extends perpendicularly from bottom surface 309B. Support wall407A extends perpendicularly from the top surface 300B of lower plate300A and connects with support wall 405A when the bottom core 201A isassembled. Conduit wall 324A may be connected to conduit 320A to form afluid tight seal and conduits 324A, 320A may be fused respectively withsupports walls 405A and 407A. Additionally present extending from thebottom surface 300C of lower plate 300A are one or more orientationspacers 409A that mate within indentation 185A.

As will be readily apparent to one of ordinary skill in the art, thebowl 10A will need to be balanced about center axis 11A. Accordingly,weights may be added as part of the device as is appropriate tofacilitate the balancing of the bowl 10A such as weight 408A illustratedin FIG. 53.

Referring to FIG. 38, bowl 10A is adapted so that outer housing 100A,cores 200A and 201A, lower plate 300A and upper plate 299A, housingfloor 180A, external conduits 20A and connection sleeve 500A, and lumens400A and 400B are in connection and rotate together. Housing floor 180Aof outer housing 100A comprises recesses 181A on its top surface andthese recesses are shaped to fit protrusion 301A of lower plate 300A. Asshown, lower plate 300A has round protrusion 301A on its bottom surface300C to restrict movement of lower plate 300A with respect to housingfloor 180A. When assembled, each single protrusion 301A on the bottomsurface of lower plate 300A forms a tight fit with recess 181A onhousing floor 180A. Thus, when outer housing 100A is rotated, externalconduit 20A and connection sleeve 500A, top core 200A, upper plate 299A,bottom core 201A, lower plate 300A, housing floor 180A, and lumens 400Aand 400B will rotate therewith.

As illustrated in FIG. 38 lumen 400A allows whole blood 800 to come intobowl 10A via a first bowl channel 420A. First bowl channel 420A providesa passageway for inflow of fluid 800 through lumen 400A to indention186A and then to the separation volume 220A through channel 305A. Lumen400A is located inside top core 200A. Lumen 400A has a height from upperlumen end 480A and lower lumen end 402C. Lumen 400A is formed by theconnection of channel wall 401A extending from the inner surface 481C oflumen connector 481A and channel wall 402A extending from the topsurface 298A of upper plate 299A. Channel wall 401A is supported by aplurality of fins 251A which are attached to the inner wall surface 210Cof the outer core wall 210A and inner surface 205C of the upper core end205A, and channel wall 402A is supported by a plurality of fins 403A(FIG. 40). It can readily be seen that height of lumen 400A can beadjusted by changing the sizes and shapes of core 200A, channel wall401A, channel wall 402A, conduit wall 325A, and the height of conduitwall 324A.

As illustrated in FIG. 38, lumen 400A, from upper lumen end 480A tolower lumen end 402C, encloses an inner lumen 400B. Lower lumen end 402Chas an opening 303A which is in fluid communication with separationvolume 220A through a number of channel 305A. In the illustratedembodiment lumen 400A comprises first bowl channel 420A. Second bowlchannel 410A is located inside first bowl channel 420A of the top core200A and is enclosed therein from lumen end 480A and to lumen 402C.Furthermore, second bowl channel 410A forms a passageway through lumen400B from below lower plate 300A for the removal of a first separatedfluid component 810 that gathers in indentation 185A of housing floor180A. Second bowl channel 410A extends from housing floor 180A of outerhousing 100A through lumen 400B and to conduit channel 760A of externalconduit 20A.

Referring FIG. 38 (shown without conduit 321C), inner lumen 400B allowsred blood cells 810 to exit bowl 10A via a second bowl channel 410A thatprovides fluid communication from the housing floor above indentation185A to opening 324E. Inner lumen 400B has an upper conduit end 325C anda lower conduit end 324B and comprises two conduit walls 324A and 325Awhich are connected in a fluid tight manner and form second bowl channel410A that has a smaller diameter than and is separate and distinct fromfirst bowl channel 420A. Conduit wall 325A is supported by a fin 251Athat extends through channel wall 401A and attaches to conduit wall325A. Unlike lumen 400A which has one end near indentation 186A, lumen400B extends beyond indentation 186A and through bottom plate 300A. Thefirst conduit wall 325A has an upper end 325C which has an opening 325Don the top surface 482A of lumen connector 481A and a lower end 325Bhaving an opening 325E adapted to fit tightly with upper end 324C ofconduit wall 324A. Upper end 324C of conduit wall 324A is higher thanindentation 186A and has an opening 324D. Conduit wall 324A also has endlower end 324B and is supported by a plurality of fins 252A. Lower end324B having opening 325E is adapted to connect to conduit 320A havingopening 302A located near the center of lower plate 300A. The connectionof openings 325E and 302A provide fluid communication between lumen 400Band the space 220C between lower plate 300A and housing floor 180A. Thespace 220C between lower plate 300A and housing floor 180A in turn hasfluid communication with separation volume 220A.

Conduit 320A provides a tight fit with lower end 324B, providing supportfor second bowl channel 410A. Each bowl channel 420A and 410A may bemade of any type of flexible or rigid tubing (such as medical tubing) orother such device providing a sealed passageway, possibly forpressurized or unpressurized fluid flow, and which preferably can bedisposable and sterilizable, i.e., of simple and efficient manufacture.

1. Drive Tube

As illustrated in FIGS. 39A and 39B, conduit assembly 860A is attachedto bowl 10A via connection sleeve 500A which is attached onto the firstend 861A of external conduit 20A having a first conduit channel 780A, asecond conduit channel 760A, and a third conduit channel 770A. Eachconduit channel has fluid communication with a first bowl channel 420A,a second bowl channel 410A, and a bowl chamber 740A. The three conduitchannels are equally spaced 120° apart and equal in diameter in externalconduit 20A (See FIG. 50). When fluidly connect to external conduit 20Aand bowl 10A, conduit channel 780A is fluidly connected with first bowlchannel 420A for inflowing fluid 800 from external conduit 20A into bowl10A for separation. Similarly, second conduit channel 760A fluidlyconnects to second bowl channel 410A for removing first separated fluidcomponent 810 from bowl 10A into external conduit 20A. Finally, thirdconduit channel 770A connects to bowl chamber 740A for removing secondseparated fluid component 820 from bowl 10A.

As is illustrated in FIG. 45, external conduit 20A has a connectionsleeve 500A on the first end 861A and an anchor sleeve 870A on thesecond end 862A of external conduit 20A. Optionally present between theconnection sleeve 500A and the anchor sleeve 870A on external conduit20A are a first shoulder 882 and a second shoulder 884 which extendperpendicularly from the external conduit 20A and are of a largerdiameter. Between the connection sleeve 500A and anchor sleeve 870A (orif present the first and second shoulder 882, 884) are a first andsecond bearing rings 871A and 872A. External conduit 20A, anchor sleeve870A, and connection sleeve may be prepared from the same or differentbiocompatible materials of suitable strength and flexibility for use inthis type of tubing in a centrifuge (one such preferred material isHYTREL®). The connection sleeve 500A and the anchor sleeve 870A may beattached through any suitable means such as adhesives, welding etc.,however, for ease of manufacture it is preferred that the connectionsleeve 500A and the anchor sleeve 870A be overmolded to the externalconduit 20A.

Referring to FIGS. 45, 48 and 49 anchor sleeve 870A comprises a body877B having a first anchor end 873A and second anchor end 874A. Anchorsleeve 870A is attached to second conduit end 862A of external conduit20A (preferably by overmolding) and increases in diameter from firstcollar 873A to the collar 874A. Spaced distally from second end 874A isa collar 886A, which extends perpendicularly from body 877B and of alarger diameter than the body 877B of the anchor sleeve 870A. Aplurality of ribs 877A having a first rib end 877B between the collar886A and second anchor end 873A and a second rib end 877C extendingbeyond the first anchor end 873A are attached to the body 877B. Thesecond rib ends 877C are joined together by a ring 880A, which is alsoattached to external conduit 20A. The ribs 877A run parallel to theexternal conduit 20A and are preferably placed over the region whereconduit channels 760A, 770A, and 780A, are closest to the surface of theexternal conduit 20A (FIG. 50). The regions where the conduit channels760A, 770A and 780A are closest to the outside diameter of externalconduit 20A unless reinforced tend to fail during high speed rotation.Having ribs parallel with the conduit channels beyond the anchor sleeveend 873A provides reinforcement to this region and prevents conduitfailure at high speed rotation. In one aspect, the ribs prevent thebuckling of the external conduit 20A in this region and act asstructural elements to transfer the torsional stress to the anchorsleeve 870A.

Connection sleeve 500A comprises body 830A having an upper sleeve end831A and lower sleeve end 832A (FIGS. 46 and 47). Lower sleeve end 832Ahas sleeve flange 790A and a plurality of protrusions 843A, which aresized to engage indentations 484A on the wall surface 482A of lumenconnector 481A. When the bowl 10A is assembled, a fluid tight seal maybe provided by placing o-ring 791A around body 830A and compressing theo-ring 791A between flange 790A and housing 100A. Upper sleeve end 831Ais adapted to be secured to external conduit 20A. Referring to FIGS. 46,39A and 39B, connection sleeve 500A is secured to bowl 10A by means ofsleeve flange 790A and is adapted to fluidly connect conduit channels780A, 760A, 770A of external conduit 20A to bowl channels 420A and 410A,and chamber 740A of bowl 10A. When assembled, connection sleeve 500A ismounted to lumen connector 481A (FIGS. 39A and 39B).

Connection sleeve 500A preferably increases in diameter from uppersleeve end 831A to lower sleeve end 832A and is overmolded to firstconduit end 861A of external conduit 20A. Connection sleeve 500Aconnects bowl 10A to external conduit 20A without use of a rotatableseal, which would otherwise normally be located between bowl 10A andconnection sleeve 500A. The seal-less connection between bowl 10A andconnection sleeve 500A may occur as explained above or alternativelythrough use of, for example, an O-ring, a groove, or lip, grommet-typeconnection, welding, or a tight fit with or without adhesive in eitherbowl 10A or connection sleeve 500A.

As illustrated in FIGS. 46 and 39B, sleeve flange 790A has a bottomsurface 847A that contacts with top surface 482A of lumen connector 481Aforming a tight seal. However, lumen connector 481A has a plurality ofindentation 483A that provides for fluid communication betweenseparation chamber 220A and bowl chamber 740A, which, in turn has fluidcommunication with conduit channel 770A. Bowl chamber 740A is defined bylumen mounting recess 851A and top surface 482A of lumen connector 481A,excluding the space occupied by hollow cylinders 321A and 322A. Aplurality of protrusions 843A on the bottom surface 847A of sleeveflange 790A engages and slides into indentations 484A on the wallsurface 482B of lumen connector 481A, thus providing a tight fit.

Connection sleeve 500A helps to secure external conduit 20A to bowl 10A,thus fluidly connecting external conduit 20A to bowl 10A. This fluidconnection enables fluid 800 to be supplied through external conduit 20Ato bowl 10A. Similarly, this fluid connection also enables separatedfluid components b, 820 to be removed from bowl 10A through externalconduit 20A.

External conduit 20A has an approximately constant diameter which helpsto reduce the rigidity. An excessively rigid external conduit 20A willheat up and fail more quickly. Additionally, a constant diameter conduitis cheap/easy to manufacture, allows easy experimentation withconnection sleeve 500A and anchor sleeve 870A sizes, and allows bearingrings 871A, 872A to be easily slid thereon. Preferably the movement ofbearings 871A and 872A will be constrained by first and second shoulders882A and 884A. External conduit 20A may be made of any type of flexibletubing (such as medical tubing) or other such device providing a sealedpassageway for the flow of fluids, which may be pressurized, into or outof a reservoir of any sort, and which preferably can be disposable andsterilizable.

II. Permanent Tower System

FIG. 17 illustrates tower system 2000. Tower system 2000 is thepermanent (i.e., non-disposable) piece of hardware that receives thevarious devices of photopheresis kit 1000, such as, cassette 1100,irradiation chamber 700, and centrifuge bowl 10 (FIG. 1). Tower system2000 performs the valving, pumping, and overall control and drive offluid flow through disposable photopheresis kit 1000. Tower system 2000performs all of the necessary control function automatically through theuse of a properly programmed controller, for example a processor or ICcircuit, coupled to all of the necessary components. While a newdisposable kit must be discarded after each photopheresis therapysession, tower system 2000 is used over and over again. Tower system2000 can be modified to perform a number of extracorporeal blood circuittreatments, for example apheresis, by properly programming thecontroller or by changing some of its components.

Tower system 2000 has a housing having an upper portion 2100 and a baseportion 2200. Base portion 2200 has a top 2201 and a bottom 2202. Wheels2203 are provided at or near the bottom 2202 of base portion 2200 sothat tower system 2000 is mobile and can easily be moved from room toroom in a hospital setting. Preferably, the front wheels 2203 arepivotable about a vertical axis to allow ease in steering andmaneuvering tower system 2000. Top 2201 of base portion 2200 has a topsurface 2204 having control deck 1200, best illustrated in FIG. 22,built therein (see FIG. 22). In FIG. 17, cassette 1100 is loaded ontocontrol deck 1200. Base portion 2200 also has hooks (not illustrated),or other connectors, to hang plasma collection bag 51 and treatment bag50 therefrom. Such hooks can be located anywhere on tower system 2000 solong as their positioning does not interfere with the functioning of thesystem during therapy. Base portion 2200 has photoactivation chamber 750(FIG. 18) located behind door 751. Additional hooks (not illustrated)are provided on tower system 2000 for hanging saline and anticoagulantbags. Preferably, these hooks are located on upper portion 2100.

Photoactivation chamber 750 (FIG. 18) is provided in base portion 2200of tower system 2000 between top 2201 and bottom 2202 behind door 751.Door 751 is hingedly connected to base portion 2200 and is provided foraccess to photoactivation chamber 750 and to allow the operator to closephotoactivation chamber 750 so that UV light does not escape into thesurrounding during treatment. Recess 752 is provided to allow tubes1112, 1117 (FIG. 1) to pass into photoactivation chamber 750 whenirradiation chamber 700 is loaded and when door 751 is closed. Thephotoactivation chamber is discussed in detail below with respect toFIGS. 16 and 18.

Upper portion 2100 is located atop base portion 2200. Centrifuge chamber2101 (FIG. 19) is located in upper portion 2100 behind centrifugechamber door 2102. Centrifuge chamber door 2102 has a window 2103 so anoperator can see in centrifuge chamber 2101 and monitor for anyproblems. Window 2103 is constructed with glass thick enough towithstand any forces that may be exerted on it from an accident duringcentrifugation which can rotate the centrifuge bowl at speeds greaterthan 4800 RPMs. Preferably, window 2103 is constructed of shatter-proofglass. Door 2102 is hingedly connected to upper portion 2100 and has anautomatic locking mechanism that is activated by the system controllerduring system operation. Centrifuge chamber 2101 is discussed below inmore detail with respect to FIG. 19.

Preferably, deck 1200 is located on top surface 2204 of base portion2200 at or near the front of system tower 2000 while upper portion 2100is extending upward from base portion 2200 near the rear of tower system2000. This allows the operator easy access to control deck 1200 whilesimultaneously affording the operator access to centrifuge chamber 2101.By designing tower system 2000 to have the centrifuge chamber 2101 inthe upper portion 2100 and having the photoactivation chamber 750 anddeck 1200 in base portion 2200, an upright configuration is achieved. Assuch, system tower 2000 has a reduced footprint size and takes up areduced amount of valuable hospital floor space. The height of systemtower 2000 remains below sixty inches so that one view is not obstructedwhen transporting the machine around the hospital form the rear.Additionally, having deck 1200 in a fairly horizontal position willprovide the operator with a place to set devices of photopheresis kit1000 during the loading of other devices, facilitating easy loading.Tower system 2000 is robust enough to withstand forces and vibrationsbrought on by the centrifugation process.

A monitor 2104 is provided on centrifuge chamber door 2102 above window2103. Monitor 2104 has a display area 2105 for visually displaying datato an operator, such as, for example, user interfaces for data entry,loading instructions, graphics, warnings, alerts, therapy data, ortherapy progress. Monitor 2104 is coupled to and controlled by thesystem controller. A data card receiving port 2001 is provided on a sideof monitor 2104. Data card receiving port 2001 is provided to slidablyreceive data card 1195 which is supplied with each disposablephotopheresis kit 1000 (FIG. 1). As mentioned above, data card 1195 canbe pre-programmed to store serve a variety of data to supply to thesystem controller of tower system 2000. For example, data card 1195 canbe programmed to relay information so that the system controller canensure: (1) that the disposable photopheresis kit is compatible with theblood drive equipment into which it is being loaded; (2) that thephotopheresis kit is capable of running the desired treatment process;(3) that the disposable photopheresis kit is of a certain brand name ormake. Data card receiving port 2001 has the necessary hardware andcircuitry to both read data from, and write data to, data card 1195.Preferably, data card receiving port 2201 will record treatment therapydata to data card 1195. Such information can include for example,collection times, collection volumes, treatment times, volumetric flowrates, any alarms, malfunctions, disturbances in the process, or anyother desired data. While data card receiving port 2001 is provided onmonitor 2104, it can be located anywhere on tower system 2000 so long asit is coupled to the system controller or other appropriate controlmeans.

A. Photoactivation Chamber for Receiving Irradiation Chamber

Referring now to FIGS. 16 and 18, photoactivation chamber 750 isillustrated in cross section. Photoactivation chamber 750 is formed byhousing 756. Housing 756 fits within base portion 2200 of tower system2000 behind door 751 (FIG. 17). Photoactivation chamber 750 has aplurality of electrical connection ports 753 provided on back wall 754.Electrical connection ports 753 are electrically coupled to a source ofelectrical energy. Photoactivation chamber 750 is designed to receiveUVA light assembly 759 (FIG. 16). When fully loaded into photoactivationchamber 750, electrical contacts (not illustrated) located on contactwall 755 of UVA light assembly 759 form an electrical connection withelectrical connection ports 753. This electrical connection allowselectrical energy to be supplied to UVA lamps 758 so that they can beactivated. Preferably, three electrical connection ports are providedfor each set of UVA lamps 758. More preferably, UVA light assembly 759has two sets of UVA lamps 758 forming a space which irradiation chamber700 can be inserted. The supply of electrical energy to UVA lamps 758 iscontrolled by the properly programmed system controller using a switch.UVA lamps 758 are activated and deactivated as necessary by thecontroller during the photopheresis therapy session.

Vent hole 757 is provided in the top of housing 756 near back wall 754of photoactivation chamber 750. Vent hole 757 connects to vent duct 760which leads out of the back of tower system 2000. When heat generated byUVA lamps 758 builds up in photoactivation chamber 750 during atreatment therapy, this heat escapes photoactivation chamber 750 viavent hole 757 and vent duct 760. The heat exits tower system 2000through tower housing hole 761 located in the rear of tower system 2000,away from the patient and the operator.

Photoactivation chamber 750 further comprises tract 762 for receivingirradiation chamber 700 and holding irradiation in an upright positionbetween UVA lamps 758. Tract 762 is at or near the bottom ofphotoactivation chamber 750. Preferably, a leak detector circuit 763 isprovided below tract 762 to detect any fluid leaks irradiation chamber700 during, before, or after operation. Leak detector circuit 762 hastwo electrodes patterned in a U shape located on an adhesive backed flexcircuit. The electrodes are designed to allow for application of a shortcircuit to test for discontinuities. One end of each electrode goes toan integrated circuit while the other end of each electrode is tied to asolid-state switch. The solid-state switch can be used to check forcontinuity of the electrodes. By closing the switch the electrodes areshorted to one another. The integrated circuit then detects the short.Closing the switch causes a situation equivalent to the electrodesgetting wet (i.e., a leak). IN If the electrodes are damaged in any way,the continuity check will fail. This is a positive indication that theelectrodes are not damaged. This test can be performed each time atsystem start-up or periodically during normal operation to ensure thatleak detection circuit 762 is working properly. Leak detection circuit762 helps ensure that leaks do not go unnoticed during an entire therapysession because the leak detection circuit is damaged. An electricalschematic of leak detector circuit 762 is provided in FIG. 20.

B. Centrifuge Chamber

FIG. 19 illustrates centrifuge chamber 2101 in cross section with thehousing of tower system 2000 removed. Rotational device 900 (also incross-section) capable of utilizing 1-omega 2-omega spin technology ispositioned within centrifuge chamber 2101. Rotational device 900includes a rotating bracket 910 and a bowl holding plate 919 forrotatably securing centrifuge bowl 10 (FIG. 1). Housing 2107 ofcentrifuge chamber 2101 is preferably made of aluminum or some otherlightweight, sturdy metal. Alternatively, other rotational systems maybe used within tower system 2000 such as that described in U.S. Pat. No.3,986,442, which is expressly incorporated herein by reference in itsentirety.

Leak detection circuit 2106 is provided on back wall 2108 of housing2107. Leak detection circuit 2106 is provided to detect any leaks withincentrifuge bowl 10 or the connecting tubes during processing. Leakdetection circuit 2106 is identical to leak detector circuit 762described above. An electrical schematic of leak detection circuit 2106is provided in FIG. 21.

C. Fluid Flow Control Deck

FIG. 22 illustrates control deck 1200 of tower system 2000 (FIG. 17)without a cassette 1100 loaded thereon. Control deck 1200 performs thevalving and pumping so as to drive and control fluid flow throughoutphotopheresis kit 1000. Preferably, deck 1200 is a separate plate 1202that is secured to base portion 2200 of tower system 2000 via screws orother securing means, such as, for example, bolts, nuts, or clamps.Plate 1202 can be made of steel, aluminum, or other durable metal ormaterial.

Deck 1200 has five peristaltic pumps, whole blood pump 1301, return pump1302, recirculation pump 1303, anticoagulant pump 1304, and red bloodcell pump 1305 extending through plate 1202. Pumps 1301-1305 arearranged on plate 1202 so that when cassette 1100 is loaded onto deck1200 for operation, pump loop tubes 1120-1124 extend over and aroundpumps 1301-1305 (FIG. 25).

Air bubble sensor assembly 1204 and HCT sensor assembly 1205 areprovided on plate 1202. Air bubble sensor assembly 1204 has threetrenches 1206 for receiving tubes 1114, 1106, and 1119 (FIG. 25). Airbubble sensor assembly 1204 uses ultrasonic energy to monitor tubes1114, 1106, and 1119 for differences in density that would indicate thepresence of air in the liquid fluids normally passing therethrough.Tubes 1114, 1106, and 1119 are monitored because these lines go to thepatient. Air bubble sensor assembly 1204 is operably coupled andtransmits data to the system controller for analysis. If an air bubbleis detected, the system controller will shut down operation and prohibitfluid flow into the patient by occluding tubes 1114, 1106, and 1109 bymoving compression actuators 1240-1242 to a raised position, therebycompressing tubes 1114, 1106, and 1119 against cassette 1100 asdiscussed above and/or shutting down the appropriate pump. HCT sensorassembly 1205 has trench 1207 for receiving HCT component 1125 of tube1116. HCT sensor assembly 1205 monitors tube 1116 for the presence ofred blood cells by using a photoelectric sensor. HCT sensor assembly1205 is also operably coupled to and transmits data to the systemcontroller. Upon HCT sensor assembly 1205 detecting the presence of redblood cells in tube 1116, the system controller will take theappropriate action, such as stopping the appropriate pump or activatingone of compression actuators 1243-1247, to stop fluid flow through tube1116.

Deck 1200 also has five compression actuators 1243-1247 and threecompression actuators 1240-1242 strategically positioned on plate 1202so that when cassette 1100 is loaded onto deck 1200 for operation, eachof compression actuators 1240-1247 are aligned with correspondingapertures 1137 and 1157. Compression actuators 1240-1247 can be movedbetween a lowered position and a raised position. As illustrated in FIG.22, compression actuators 1243-1247 are in the lowered position andcompression actuators 1240-1242 are in the raised position. When in araised position, and when cassette 1100 is loaded onto deck 1200 asillustrated in FIG. 25, compression actuators 1240-1247 will extendthrough the corresponding apertures 1137 or 1157 and compress theportion of flexible tubing that is aligned with that aperture, therebypinching the flexible tube shut so that fluid can not pass. When in thelowered position, compression actuators 1240-1247 do not extend throughapertures 1137 and 1157 and thus do compress the flexible tubing.

Compression actuators 1243-1247 are spring retracted so that theirdefault position is to move to the lowered position unless activated.Compression actuators 1243-1247 are independently controlled and can beraised r lowered independent of one another. Compression actuators1240-1242 on the other hand are coupled together. As such, when onecompression actuator 1240-1242 is lowered or raised, the other twocompression actuators 1240-1242 are also lowered in raised accordingly.Additionally, compression actuators 1240-1242 are spring loaded so thattheir default position is to move to the raised position. Thus, if thesystem loses power during a therapy session, compression actuators1240-1242 will automatically move to the raised position, occludingtubes 1114, 1106, and 1119 and preventing fluids from entering orleaving the patient.

Referring now to FIGS. 23 and 24, deck 1200 further includes systemcontroller 1210, cylinder assembly 1211, manifold assemblies 1213, pumpcable 1215, pump motor cable 1216, and timing belt assembly 1217. Systemcontroller 1210 is a properly programmed integrated circuit that isoperably coupled to the necessary components of the system to performall of the functions, interactions, decisions, and reaction discussedabove and necessary to perform a photopheresis therapy according to thepresent invention. Cylinder assembly 1211 couples each of compressionactuators 1240-1247 to a pneumatic cylinder. Air ports 1212 are providedon the various elements of deck 1200 as necessary to connect air linesto the devices and the appropriate one of manifolds 1213. As such, aircan be provided to the devices as necessary to actuate the necessarycomponent, such as compression valves 1240-1247. All of these functionsand timing are controlled by system controller 1210. Timing beltassembly 1217 is used to coordinate the rotation of rotating clamps1203. Finally, plate 1202 includes a plurality of holes 1215, 1219,1220, 1221, and 1218 so that the various components of deck 1200 can beproperly loaded into and so that deck 1200 can be secured to towersystem 2000. Specifically, pumps 1301-1305 fit into holes 1314, HCTsensor assembly 1205 fits into hole 1220, air bubble detector assembly1204 fits into hole 1219, compression actuators 1240-1247 extend throughholes 1218, and bolts extend through holes 1221 to secure deck 1200 totower assembly 2000.

1. Cassette Clamping Mechanism

Referring now to FIGS. 22 and 25, the method by which cassette 1100 isloaded and secured to deck 1200 will now be discussed. In order forsystem 2000 to perform a photopheresis therapy, cassette 1100 must beproperly loaded onto deck 1200. Because of the compression actuatorvalving system incorporated in the present invention, it is imperativethat cassette 1100 be properly secured to deck 1200 and not shift orbecome dislodged when compression actuators 1240-1247 occlude portionsof the flexible tubing by compressing the flexible tubing against cover1130 of cassette 1100 (FIG. 3). However, this requirement competes withthe desired goals of ease in loading cassette 1100 onto deck 1200 andreducing operator errors. All of these goals are achieved by the belowdescribed cassette clamping mechanism.

In order to facilitate clamping of cassette 1100 to deck 1200, deck 1200is provided with two catches 1208 and two rotating clamps 1203 and 1223.Catches 1208 have a slot 1228 near the middle of the top plate. Catches1208 are secured to plate 1202 at predetermined positions so that thespacing between them is substantially the same as the spacing betweentabs 1102 and 1103 on cassette 1100 (FIG. 2). Rotating clamps 1203 and1223 are illustrated in a closed position. However, rotating clamps 1203and 1223 can be rotated to an open position (not illustrated) manuallyor through the automatic actuation of a pneumatic cylinder. Rotatingclamps 1203 and 1223 are spring loaded by torque springs so as toautomatically return to the closed position when additional torque isnot being applied. Rotating clamps 1203 and 1223 are linked together bytiming belt assembly 1217 (FIG. 24).

Referring now to FIG. 23, timing belt assembly 1217 comprises timingbelt 1226, torque spring housings 1224, and tension assembly 1225.Timing belt assembly 1217 coordinates the rotation of rotational clamps1203 and 1223 so that if one is rotated, the other also rotates in thesame direction and the same amount. In other words, rotational clamps1203 and 1223 are coupled. Tension assembly 1217 ensures that timingbelt 1226 is under sufficient tension to engage and rotate therotational clamp 1203 or 1223 that is being coordinated. Torque springhousings 1224 provide casings for the torque springs that torquerotational clamps 1203 and 1223 to the closed position.

Referring back to FIGS. 22 and 25, when loading cassette 1100 onto deck1200, cassette 1100 is placed at an angle to deck 1200 and tabs 1102 and1103 (FIG. 2) are aligned with catches 1208. Cassette 1100 is moved sothat tabs 1102 and 1103 slidably insert into catches 1208. Rotationalclamps 1203 and 1223 are in the closed position at this time. The rearof the cassette 1100 (i.e. the side opposite the tabs 1102 and 1103)contacts rotational clamps 1203 and 1223 as tabs 1102 and 1103 are beinginserted in catches 1108. As force is applied downward on cassette 1100,rotational clamps 1103 and 1123 will be rotated to the open position,allowing the rear of cassette 1100 to move downward to a position belowledges 1231 of rotational clamps 1203 and 1223. Once cassette 1100 is inthis position, the rotational clamps 1203 and 1223 spring back from theforce applied by the torque springs and rotate back to the closedposition, locking cassette 1100 in place. When in the locked position,cassette 1100 can resist upward and lateral forces.

To remove cassette 1110 after the therapy session is complete,rotational clamps 1203 and 1223 are rotated to the open position eithermanually or automatically. Automatic rotation is facilitated by an aircylinder that is coupled to an air line and system controller 1210. Oncerotational clamps 1203 and 1223 are in the open position, cassette 1100is removed by simple lifting and sliding tabs 1102 and 1103 out ofcatches 1208.

2. Self-Loading Peristaltic Pumps

Referring to FIG. 24, peristaltic pumps 1301-1305 are provided on deck1200 and are used to drive fluids through photopheresis kit 1000(FIG. 1) along desired pathways. The activation, deactivation, timing,speed, coordination, and all other functions of peristaltic pumps1301-1305 are controlled by system controller 1210. Peristaltic pumps1301-1305 are identical in structure. However, the placement of eachperistaltic pump 1301-1305 on deck 1200 dictates the function of eachperistaltic pump 1301-1305 with respect to which fluid is being drivenand along which pathway. This is because the placement of peristalticpumps 1301-1305 dictates which pump loop 1220-1224 will be loadedtherein.

Referring now to FIGS. 28 and 29, whole blood pump 1301 is illustratedin detail. The structure and functioning of whole blood pump will bedescribed with the understanding that peristaltic pumps 1302-1305 areidentical. Whole blood pump 1301 has motor 1310, position sensor 1311,pneumatic cylinder 1312, pneumatic actuator 1313, rotor 1314 (bestillustrated in FIG. 30), and housing 1315.

Rotor 1314 is rotatably mounted within housing 1315 and is in operableconnection with drive shaft 1316 of motor 1310. Specifically, rotor 1314is mounted within curved wall 1317 of housing 1315 so as to be rotatableby motor 1310 about axis A-A. When rotor 1314 is mounted in housing1315, a space 1318 exists between rotor 1314 and curved wall 1317. Thisspace 1318 is the tube pumping region of whole blood pump 1301 intowhich pump loop tube 1121 (FIG. 33) fits when loaded for pumping.Position sensor 1316 is coupled to drive shaft 1316 of motor 1310 sothat the rotational position of rotor 1314 can be monitored bymonitoring drive shaft 1316. Position sensor 1311 is operably connectedand transmits data to system controller 1210 (FIG. 24). By analyzingthis data, system controller 1210, which is also coupled to motor 1310,can activate motor 1310 to place rotor 1314 in any desired rotationalposition.

Housing 1315 also includes a housing flange 1319. Housing flange 1319 isused to secure whole blood pump 1310 to plate 1202 of deck 1200 (FIG.22). More specifically, a bolt is extended through bolt holes 1320 ofhousing flange 1319 to threadily engage holes within plate 1202. Housingflange 1319 also includes a hole (not shown) to allow pneumatic actuator1313 to extend therethrough. This hole is sized so that pneumaticactuator 1313 can move between a raised and lowered position withoutconsiderable resistance. Pneumatic actuator 1313 is activated anddeactivated by pneumatic cylinder 1312 in a piston-like manner throughthe use of air. Pneumatic cylinder 1312 comprises air inlet hole 1321for connecting an air supply line. When air is supplied to pneumaticcylinder 1312, pneumatic actuator extends upward through housing flange1319 to a raised position. When air ceases to be supplied to pneumaticcylinder 1312, pneumatic actuator retracts back into pneumatic cylinder1312, returning to the lowered position. System controller 1210 (FIG.22) controls the supply of air to air inlet hole 1321.

Curved wall 1317 of housing 1315 contains two slots 1322 (only onevisible). Slots 1322 are located on substantially opposing sides ofcurved wall 1317. Slots 1322 are provided for allowing pump loop tube1121 (FIG. 33) to pass into tube pumping region 1318. More specifically,pump inlet portion 1150 and outlet portions 1151 (FIG. 33) of pump looptube 1121 pass through slots 1322.

Turning now to FIGS. 30 and 31, rotor 1314 is illustrated as removedfrom housing 1315 so that its components are more clearly visible. Rotor1314 has a top surface 1323, angled guide 1324, rotor flange 1325, twoguide rollers 1326, two drive rollers 1327, and rotor floor 1328. Guiderollers 1326 and drive rollers 1327 are rotatably secured about cores1330 between rotor floor 1328 and a bottom surface 1329 of rotor flange1325. As is best illustrated in FIG. 29, cores 1330 fit into holes 1331of rotor floor 1328 and recesses 1332 in bottom surface 1329. Guiderollers 1326 and drive rollers 1327 fit around cores 1330 and can rotatethereabout. Preferably, two guide rollers 1326 and two drive rollers1327 are provided. More preferably, guide rollers 1326 and drive rollers1327 are provided on rotor 1314 so as to be in an alternating pattern.

Referring to FIGS. 29 and 31, drive rollers 1327 are provided tocompress the portion of pump loop tube 1121 that is loaded into tubepumping region 1318 against the inside of curved wall 1317 as rotor 1314rotates about axis A-A, thereby deforming the tube and forcing fluids toflow through the tube. Changing the rotational speed of rotor 1314 willcorrespondingly change the rate of fluid flow through the tube. Guiderollers 1326 are provided to keep the portion of pump loop tube 1121that is loaded into tube pumping region 1318 properly aligned duringpumping. Additionally, guide rollers 1326 help to properly load pumptube loop 1121 into tube pumping region 1318. While guide rollers 1326are illustrated as having a uniform cross-section, it is preferred thatthe top plate of the guide rollers be tapered so as to come to a sharperedge near its outer diameter. Tapering the top plate results in a guideroller with a non-symmetric cross-sectional profile. The taperedembodiment helps ensure proper loading of the tubing into the tubepumping region.

Rotor 1314 further includes cavity 1328 extending through its center.Cavity 1328 is designed to connect rotor 1314 to drive shaft 1316 ofmotor 1310.

Referring now to FIGS. 30 and 32, rotor flange has opening 1333. Opening1333 is defined by a leading edge 1334 and a trailing edge 1335. Theterms leading and trailing are used assuming that rotating rotor 1314 inthe clockwise direction is the forward direction while rotating rotor1314 in a counterclockwise direction is the rearward direction. However,the invention is not so limited and can be modified for counterclockwisepumps. Leading edge 1334 is beveled downward into opening 1333. Trailingedge 1335 extends upward from the top surface of rotor flange 1325higher than the leading edge 1334. Leading edge is provide for trailingedge for capturing and feeding pump loop tube 1121 into tube pumpingregion 1318 upon rotor 1314 being rotated in the forward direction.

Rotor 1314 also has angled guide 1324 extending upward, at an invertedangle, from rotor flange 1325. Angled guide 1324 is provided fordisplacing pump loop tube 1121 toward rotor flange 1325 upon rotor 1314being rotated in the forward direction. Preferably, angled guide 1324has elevated ridge 1336 running along top surface 1323 for manualengagement by an operator if necessary. More preferably, angled guide1314 is located forward of leading edge 1334.

Referring now to FIGS. 28 and 33, whole blood pump 1301 canautomatically load and unload pump lop tube 1121 into and out of tubepumping region 1318. Using position sensor 1311, rotor 1314 is rotatedto a loading position where angled guide 1324 will face cassette 1100when cassette 1100 is loaded onto deck 1200 (FIG. 25). Morespecifically, rotor 1314 is preset in a position so that angled guide1324 is located between inlet portion 1150 and outlet portion 1151 ofpump loop 1121 when cassette 1100 is secured to the deck, as isillustrated in FIG. 13. When cassette 1100 is secured to deck 1200, pumplop tube 1121 extends over and around rotor 1314. Pneumatic actuator1313 is in the lowered position at this time.

Once cassette 1100 is properly secured and the system is ready, rotor1314 is rotated in the clockwise direction (i.e., the forwarddirection). As rotor 1314 rotates, pump tube loop 1121 is contacted byangled guide 1324 and displaces against the top surface of rotor flange1325. The portions of pump loop tube 1121 that are displaced againstrotor flange 1325 are then contacted by trailing edge 1325 and feddownward into tube pumping region 1318 through opening 1333. A guideroller 1326 is provided directly after opening 1333 to further properlyposition the tubing within tube pumping chamber for pumping by driverollers 1327. When loaded, inlet portion 1150 and outlet portion 1151 ofpump loop tube 1121 pass through slots 1322 of curved wall 1317. One anda half revolutions are needed to fully load the tubing.

To automatically unload pump tube loop 1121 from whole blood pump 1301after the therapy is complete, rotor 1314 is rotated to a position whereopening 1333 is aligned with the slot 1322 through which outlet portion1151 passes. Once aligned, pneumatic actuator 1313 is activated andextended to the raised position, contacting and lifting outlet portion1151 to a height above trailing edge 1335. Rotor 1314 is then rotated inthe counterclockwise direction, causing trailing edge to 1335 to contactand remove pump loop tube 1121 from tube pumping region 1318 via opening1333.

D. Infra-Red Communication

Referring to FIG. 34, tower system 2000 (FIG. 17) preferably furtherincludes a wireless infrared (“IR”) communication interface (not shown).The wireless IR interface consists of three primary elements, systemcontroller 1210, IRDA protocol integrated circuit, 1381, and IRDAtransceiver port 1382. The IR communication interface is capable of bothtransmitting and receiving data via IR signals from a remote computer orother device having IR capabilities. In sending data, system controller1210 sends serial communication data to the IRDA protocol chip 1381 tobuff the data. IRDA protocol chip 1381 adds additional data and othercommunication information to the transmit string and then sends it toIRDA transceiver 1382. Transceiver 1382 converts the electrical transmitdata into encoded light pulses and transmits them to a remote device viaa photo transmitter.

In receiving data, IR data pulses are received by a photo detectorlocated on the transceiver chip 1382. The transceiver chip 1382 convertsthe optical light pulses to electrical data and sends the data stream toIRDA protocol chip 1381 where the electrical signal is stripped ofcontrol and additional IRDA protocol content. The remaining data is thensent to the system controller 1210 where the data stream is parsed perthe communication protocol.

By incorporating an IR communication interface on tower system 2000 realtime data relating to a therapy session can be transmitted to a remotedevice for recording, analysis, or further transmission. Data can besent via IR signals to tower system 2000 to control the therapy or allowprotocols to be changed in a blinded state. Additionally, IR signals donot interfere with other hospital equipment, like other wirelesstransmission methods, such as radio frequency.

III. Photopheresis Treatment Process

Referring together to FIG. 26, a flow chart illustrating an embodimentof the invention which includes photactivation of buffy coat, and FIG.27, a schematic representation of apparatus which can be employed insuch an embodiment, the process starts 1400 with a patient 600 connectedby means of a needle adapter 1193 carrying a needle, for drawing blood,and needle adapter 1194 carrying another needle, for returning treatedblood and other fragments. Saline bag 55 is connected by connector 1190and anticoagulant bag 54 is connected by connector 1191. Actuators 1240,1241, and 1242 are opened, anticoagulant pump 1304 is turned on, andsaline actuator 1246 is opened so that the entire disposable tubing setis primed 1401 with saline 55 and anticoagulant 54. The centrifuge 10 isturned on 1402, and blood-anticoagulant mixture is pumped 1403 to thecentrifuge bowl 10, with the A/C pump 1304 and WB pump 1301 controlledat a 1:10 speed ratio.

When the collected volume reaches 150 ml 1404, the return pump 1302 isset 1405 at the collection pump 1301 speed until red cells are detected1406 at an HCT sensor (not shown) in the centrifuge chamber 1201 (FIG.19). Packed red cells and buffy coat have at this point accumulated inthe spinning centrifuge bowl and are pumped out slowly at a rate,controlled by the processor, which maintains the red cell line at thesensor interface level.

The red cell pump 1305 is then set 1407 at 35% of the inlet pump speedwhile controlling 1408 the rate to maintain the cell line at theinterface level until the collection cycle volume is reached 1409, atwhich point the red cell pump 1305 is turned off 1410 and the fluid pathto the treatment bag 50 via the HCT sensor 1125 is opened by loweringactuator 1244, and stops when the HCT sensor 1125 detects 1411 redcells. “Collection cycle volume” is defined as the whole blood processedtarget divided by the number of collection cycles, for example a whiteblood process target of 1500 ml may require 6 cycles, and so 1500/6 is avolume of 250 ml. With whole blood continuing at 1410 to be deliveredfrom the patient to the bowl and the red cell pump off, red cells willaccumulate and will push out the buffy coat from inside the bowl 10. Thered cells are used to push out the buffy coat and will be detected bythe effluent hematocrit (HCT) sensor, indicating that the buffy coat hasbeen collected.

If another cycle is needed 1412, the centrifuge 10 effluent path isreturned 1413 to the plasma bag 51 and the red cell pump 1305 rate isincreased 1413 to the inlet pump 1301 pump rate until red cells aredetected 1414, which is the beginning of the second cycle. If anothercycle 1412 is not needed, the centrifuge 10 is turned off 1415 and inletpump 1301 and anticoagulant pump 1304 are set at KVO rate, 10 ml/hr inthis embodiment. The effluent path is directed 1416 to the plasma bag51, the red cell pump 1305 rate is set 1417 at 75 ml/min, therecirculation pump 1303 and photoactivation lamps are turned on 1418 forsufficient period to treat the buffy coat, calculated by the controllerdepending on the volume and type of disease being treated.

When the bowl 10 is empty 1419, the red cell pump 1305 is turned off1420 and the plasma bag 51 is emptied 1421 by opening actuator 1247 andcontinuing return pump 1302. The return pump 1302 is turned off 1422when the plasma bag 51 is empty and when photoactivation is complete1423, the treated cells are returned 1424 to the patient from the plate700 by means of the return pump 1302. Saline is used to rinse the systemand the rinse is returned to the patient, completing the process 1425.

The anticoagulant, blood from patient, and fluid back to patient are allmonitored by air detectors 1204 and 1202, and the fluid back to thepatient goes through drip chamber and filter 1500. The pumps, 1304,1301, 1302, 1303, and 1305, the actuators 1240, 1241, 1242, 1243, 1244,1245, 1246, and 1247, and the spinning of the bowl 10 are all controlledby the programmed processor in the tower.

The process and related apparatus have significant advantages over priorprocesses and apparatus in that the invention allow buffy coat to be inthe bowl longer since red cells are being drawn off while collectingbuffy coat in the bowl while centrifuging, keeping more buffy coat inthe bowl until the desired amount of buffy coat cells are collectedprior to withdrawing the collected buffy cells. Platelets, leukocytes,and other buffy coat fractions can also be separated, or red cells canbe collected rather than returning them with plasma to the patient asthe illustrated process does.

It has been found that increasing the time that buffy coat 810 issubjected to rotational motion in centrifuge bowl 10 yields a “cleanercut” of buffy coat 820. A “cleaner cut” means that the hematocrit count(HCT %) is decreased. HCT % is the amount of red blood cells present pervolume of buffy coat. The amount of time that buffy coat 820 issubjected to rotational motion in centrifuge bowl 10 can be maximized inthe following manner. First, whole blood 800 is fed into first bowlchannel 420 as centrifuge bowl 10 is rotating. As discussed above, wholeblood 800 is separated into buffy coat 820 and RBC's 810 as it movesoutwardly atop lower plate 300. Second bowl channel 410 and third bowlchannel 740 are closed at this time. The inflow of whole blood 800 iscontinued until the separation volume 220 is filled with a combinationof buffy coat 820 near the top and RBC's 810 near the bottom ofcentrifuge bowl 10. By removing RBC's 810 from centrifuge bowl 10 viasecond bowl channel 410 only, additional volume is created for theinflow of whole blood 800 and the unremoved buffy coat 820 is subjectedto rotational forces for an extended period of time. As centrifuge bowl10 continues to rotate, some of the RBC's 810 that may be trapped inbuffy coat 820 get pulled to the bottom of centrifuge bowl 10 and awayfrom third bowl channel 740 and buffy coat 820. Thus, when third bowlchannel 740 is opened, the buffy coat 820 that is removed has a lowerHCT %. By controlling the inflow rate of whole blood 800 and the outflowrates of buffy coat 820 and RBC's 810, a steady state can be reachedthat yields a buffy coat 820 with an approximately constant HCT %.

The elimination of batch processing and the improved yields achieved bythe current invention, have reduced the treatment time necessary toproperly treat patients. For an average sized adult, 90-100 millilitersof buffy coat/white blood cells must be captured in order to conduct afull photopheresis treatment. In order to collect this amount of buffycoat/white blood cells, the present invention needs to process around1.5 liters of whole blood. The required amount of buffy coat/white bloodcells can be removed from the 1.5 liters of whole blood in about 30-45minutes using the present invention, collecting around 60% or more ofthe total amount of the buffy coat/white blood cells that are subjectedto the separation process. The captured buffy coat/white blood cellshave an HCT of 2% or less. In comparison, one existing apparatus, theUVAR XTS, takes around 90 minutes to process 1.5 liters of whole bloodto obtain the sufficient amount of buffy coat/white blood cells. TheUVAR XTS only collects around 50% of the total amount of the buffycoat/white blood cells that are subjected to the separation process. TheHCT of the buffy coat/white blood cells collected by the UVAR XTS isaround, but not substantially below, 2%. Another existing apparatus, theCobe Spectra™ by Gambro, must process 10 liters of whole blood in orderto collect the sufficient amount of buffy coat/white blood cells. Thistypically takes around 150 minutes, collecting only 10-15% of the totalamount of the buffy coat/white blood cells that are subjected to theseparation process, and having an HCT of about 2%. Thus, it has beendiscovered that while existing apparatus and systems require anywherefrom 152 to 225 minutes to separate, process, treat, and reinfuse therequisite amount of white blood cells or buffy coat, the presentinvention can perform the same functions in less than 70 minutes. Thesetimes do not include the patient preparation or prime time. The timesindicate only the total time that the patient is connected to thesystem.

1. A kit for use in a device for separating biological fluids into morethan one component comprising: a cassette for directing the flow ofbiological fluids through said device, a bowl in which said separationis conducted, tubing for movement of said biological fluid, and two ormore needle adapters wherein one of said needle adapters is forwithdrawing said biological fluid from a patient and at least one otheris for returning one or more components to the patient.
 2. The kit ofclaim 1 further including a package for containing said kit.
 3. The kitof claim 1 further including instructions for the use of the kit inblood separation.
 4. The kit of claim 1 further including instructionsfor the use of the kit in therapeutic applications.
 5. The kit of claim4 wherein the therapeutic applications include the use of a therapeuticagent.
 6. The kit of claim 4 wherein the therapeutic application istreatment with light.
 7. The kit of claim 4 wherein the therapeuticapplication is extracorporeal photopheresis.
 8. The kit of claim 7further comprising an irradiation chamber, hematocrit sensor, data card,treatment bag, and collection bag.
 9. A kit for use in a device forseparating biological fluids into more than one component comprising: acassette for directing the flow of biological fluids through saiddevice, a centrifuge bowl in which said separation is conducted, anirradiation chamber, a treatment bag, a collection bag, tubing formovement of said biological fluid, and two or more needle adapterswherein one of said needle adapters is for withdrawing said biologicalfluid from a patient and at least one other is for returning one or morecomponents to the patient.
 10. The kit of claim 9 further including apackage for containing said kit.
 11. The kit of claim 9 wherein thetherapeutic application is treatment with light.
 12. The kit of claim 11wherein the therapeutic application is extracorporeal photopheresis. 13.The kit of claim 9 further comprising a hematocrit sensor and a datacard.
 14. The kit of claim 9 further comprising a photoactive compound.15. An apparatus comprising a disposable kit, the kit comprising acassette; a saline bag inlet tube; a treatment bag; a plasma collectionbag having an inlet tube for flowing plasma from the cassette and anoutlet tube for flowing plasma to the cassette; an anticoagulant inlettube for flowing anticoagulant to the cassette; an irradiation chamberhaving an inlet tube for flowing buffy coat from the cassette and anoutlet tube for flowing irradiated buffy coat to the cassette; aseparation bowl having one tube for flowing blood to the separationchamber and at least two tubes for flowing separate blood fragments fromthe separation chamber; means to withdraw blood from a patientcomprising a tube for flowing blood to the cassette; and means to returnblood fractions to the patient comprising a tube from the cassette, andtwo or more needle adapters wherein one of said needle adapters is forwithdrawing said biological fluid from a patient and at least one otheris for returning one or more components to the patient.
 16. The kit ofclaim 15 further comprising a hematocrit sensor and a data card.
 17. Thekit of claim 15 further comprising a photoactive compound.
 18. The kitof claim 15 further comprising a therapeutic compound.
 19. The kit ofclaim 15 further comprising two needles.
 20. The kit of claim 15 furthercomprising instructions for arranging said kit for either single ordouble needle treatment and for switching the configuration of sucharrangements from single to double needle or from double to singleneedle.